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1.
Biomolecules ; 15(1)2025 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-39858504

RESUMO

Aromatic plants are rich sources of essential oils (EOs), recognized for their therapeutic properties due to their diversity of phytochemicals. This study investigated the anxiolytic and antidepressant effects of Myrcia sylvatica essential oil (MsEO) through inhalation in an animal model and its in vitro anticholinesterase (AChE) activity. The EO was obtained by hydrodistillation, and its volatile constituents were analyzed by GC-MS. Swiss mice were exposed to doses of 0.1%, 1%, and 2% of the EO via an inhalation apparatus. The anxiolytic activity was assessed using the elevated plus maze and light-dark box tests, while antidepressant activity was evaluated using the tail suspension and forced swimming tests. To examine potential side effects, the animals were subjected to rotarod, Y-maze, and Morris water maze tests to assess motor coordination, memory, and learning. Anticholinesterase activity was determined by direct bioautography and colorimetry based on the Ellman method. The results demonstrated that inhalation of MsEO at doses of 0.1% and 1% significantly reduced anxiety and depressive-like behaviors without impairing memory, learning, or motor coordination in the animals. Moreover, MsEO inhibited acetylcholinesterase with an IC50 of 0.47 µg/mL. These findings suggest that MsEO has potential therapeutic applications for anxiety and depression disorders, with additional anticholinesterase activity warranting further investigation in cognitive-related conditions.


Assuntos
Ansiolíticos , Antidepressivos , Inibidores da Colinesterase , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Camundongos , Ansiolíticos/farmacologia , Ansiolíticos/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Antidepressivos/farmacologia , Antidepressivos/química , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico
2.
Mol Neurobiol ; 62(1): 674-692, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38898198

RESUMO

Alzheimer's Disease is a degenerative neurological condition which leads to a decline in memory and cognitive function. Chlorogenic Acid (CGA) presents properties including neuroprotective, antioxidant and anti-inflammatory. The aim of this study was to examine the impact of CGA on cognitive impairments, neuroinflammation and neuronal damage in mice submitted to an experimental model of Sporadic Alzheimer Disease (SAD) induced by intracerebroventricular administration of streptozotocin (ICV-STZ). Male Swiss mice received bilateral ICV-STZ injections (3 mg/Kg) on days 1 and 3. The treatment with CGA (5 mg/Kg, orally) or vehicle (water, orally), was initiated and continued for 26 days, starting 2 h after the second induction procedure. At first, there was no change in serum glucose levels after SAD induction. ICV-STZ induces impairments in aversive, recognition, and spatial memory, while CGA treatment significantly alleviated these memory deficits. Furthermore, locomotor activity, working memory, and anxiety-related activities remained unaffected by the treatments. CGA treatment protects against ICV-STZ-induced increase in the nitrite/nitrate and TBARS levels. ICV-STZ induced a reduction in viable cells, depletion of BDNF, and triggered astrogliosis and microgliosis in the cortex and hippocampus. Treatment with CGA preserves viable cell count in the prefrontal cortex, CA1, and CA3 regions of the hippocampus. Additionally, it prevented BDNF depletion in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions), and mitigated astrogliosis and microgliosis in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions). These findings indicate the neuroprotective effects of CGA, underscoring their potential as therapeutic agents or adjuncts in the treatment of SAD.


Assuntos
Doença de Alzheimer , Ácido Clorogênico , Modelos Animais de Doenças , Fármacos Neuroprotetores , Estreptozocina , Animais , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Estreptozocina/toxicidade , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Doença de Alzheimer/induzido quimicamente , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos
3.
Int J Mol Sci ; 25(21)2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39518888

RESUMO

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children.


Assuntos
Diabetes Mellitus Experimental , Hipocampo , Memória , Animais , Diabetes Mellitus Experimental/patologia , Ratos , Gravidez , Feminino , Hipocampo/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Masculino , Diabetes Gestacional/patologia , Estreptozocina , Ratos Wistar , Células Piramidais/patologia , Células Piramidais/metabolismo , Aprendizagem , Aprendizagem em Labirinto
4.
Neurochem Res ; 50(1): 8, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39546064

RESUMO

The decline in cognitive function associated with aging significantly impacts the well-being of elderly individuals and their families. This decline is a major recognized risk factor for neurodegenerative diseases, notably Alzheimer's disease. Animal models of aging provide a platform for evaluating drugs concerning aspects like memory and oxidative stress. JM-20 has demonstrated protective effects on short-term memory acquisition and consolidation, along with antioxidant properties and modulation of Acetylcholinesterase activity. This study assesses the potential protective JM-20 against cognitive decline and age-related memory loss. For the study, aged mice exhibiting aging-associated damage were initially selected. Experimental groups were then formed, and the effect of 8 mg/kg of JM-20 was evaluated for 40 days on aging-related behavior, such as spatial memory, novelty recognition memory, ambulatory activity, and anxiety. Subsequently, animals were sacrificed, and the hippocampal region was extracted for redox studies and to assess acetylcholinesterase activity. Results indicated that JM-20 at 8 mg/kg reversed damage to spatial working and reference memory, exhibiting performance comparable to untreated young adult animals. Furthermore, JM-20 preserved the enzymatic activity of superoxide dismutase, catalase, and total sulfhydryl levels in age-related cognitive impairment in mice, indicating a potent protective effect against oxidative events at the brain level. However, only young, healthy animals showed decreased acetylcholinesterase enzyme activity. These findings provide preclinical pharmacological evidence supporting the neuroprotective activity of JM-20, positioning it as a promising therapeutic candidate for treating memory disorders associated with aging.


Assuntos
Envelhecimento , Disfunção Cognitiva , Animais , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Envelhecimento/metabolismo , Envelhecimento/efeitos dos fármacos , Masculino , Acetilcolinesterase/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Memória Espacial/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos
5.
Anim Cogn ; 27(1): 72, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39485623

RESUMO

Rats and pigeons have shown striking differences in their behavior in the suboptimal choice procedure: while pigeons show a strong and consistent preference for the discriminative alternative, most studies performed with rats have found optimal preferences, and in the cases in which suboptimal preferences have been reported, those results have not been replicated. Currently, there is no consensus about the reasons for these discrepant results between species, but different explanations have been proposed either with an empirical base or exclusively in theoretical terms. In the latter category it has been proposed that the discrepancy might have arisen because of differences in the relationship between the natural foraging response of each species, and the response required in the laboratory. For analyzing this possibility, we conducted two experiments carried out within a maze that was specifically designed to allow rats to display behaviors related to their natural foraging. In experiment 1, we explored rats' preferences when facing a discriminative alternative with probability of reinforcement (p) = 0.5, and a non-discriminative alternative with p = .75. In experiment 2, we evaluated preferences when the discriminative alternative had p = .20 and the non-discriminative had p = .50, rats were evaluated in a closed economy, with longer terminal links, and were allowed to escape from the outcome found. In both studies, rats showed a strong preference for the non-discriminative alternative and showed very high levels of discrimination between the positive and the negative outcomes of the discriminative alternative.


Assuntos
Comportamento de Escolha , Animais , Ratos , Masculino , Aprendizagem em Labirinto , Aprendizagem por Discriminação , Reforço Psicológico
6.
Neuromolecular Med ; 26(1): 31, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073519

RESUMO

The aim of this study was to evaluate the effects of swimming in the brain and behavior of young and aged mice. Forty-eight male C57BL/6 J mice were randomly distributed into 4 groups (n = 12 per group, 3 and 18 months old). The subdivision of the groups was: 3 months-SED, 18 months-SED, 3 months-EXE, and 18 months-EXE. SED mice did not swim, while EXE mice performed the physical exercise protocol. Training was initiated 48 h after the adaptation week. Swimming sessions consisted of 30 min, with no overload, 5 days per week, for 4 weeks. After the exercise protocol, it was revealed working and spatial memory were impaired in the 18 months-SED group. Pre- and post-synaptic proteins were enhanced in the groups that swam when compared to the 3- and 8 months-SED groups. Lipid peroxidation was greater in the aged mice that did not perform the physical exercise protocol and might have contributed to the cognitive impairment in this group. In conclusion, an aerobic physical exercise protocol, performed through regular swimming sessions, inhibited cognitive impairment, memory loss and lipid peroxidation in the aged mice, while pre- and post-synaptic proteins were enhanced in the hippocampus of young and aged mice.


Assuntos
Envelhecimento , Hipocampo , Peroxidação de Lipídeos , Transtornos da Memória , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal , Natação , Animais , Masculino , Camundongos , Hipocampo/metabolismo , Envelhecimento/fisiologia , Transtornos da Memória/etiologia , Transtornos da Memória/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/etiologia , Proteínas do Tecido Nervoso/biossíntese , Memória Espacial/fisiologia , Aprendizagem em Labirinto , Memória de Curto Prazo/fisiologia , Proteína 4 Homóloga a Disks-Large/metabolismo , Sinaptofisina/metabolismo
7.
ACS Chem Neurosci ; 15(16): 2982-2994, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39007352

RESUMO

Alzheimer's disease (AD) is a complex neurodegenerative process, also considered a metabolic condition due to alterations in glucose metabolism and insulin signaling pathways in the brain, which share similarities with diabetes. This study aimed to investigate the therapeutic effects of benfotiamine (BFT), a vitamin B1 analog, in the early stages of the neurodegenerative process in a sporadic model of Alzheimer's-like disease induced by intracerebroventricular injection of streptozotocin (STZ). Supplementation with 150 mg/kg of BFT for 7 days reversed the cognitive impairment in short- and long-term memories caused by STZ in rodents. We attribute these effects to BFT's ability to modulate glucose transporters type 1 and 3 (GLUT1 and GLUT3) in the hippocampus, inhibit GSK3 activity in the hippocampus, and modulate the insulin signaling in the hippocampus and entorhinal cortex, as well as reduce the activation of apoptotic pathways (BAX) in the hippocampus. Therefore, BFT emerges as a promising and accessible intervention in the initial treatment of conditions similar to AD.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Hipocampo , Insulina , Transdução de Sinais , Estreptozocina , Tiamina , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Tiamina/farmacologia , Tiamina/análogos & derivados , Tiamina/uso terapêutico , Ratos , Cognição/efeitos dos fármacos , Ratos Wistar , Aprendizagem em Labirinto/efeitos dos fármacos
8.
Biochem Pharmacol ; 226: 116339, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38848781

RESUMO

Sleep is a fundamental state for maintaining the organism homeostasis. Disruptions in sleep patterns predispose to the appearance of memory impairments and mental disorders, including depression. Recent pre-clinical studies have highlighted the antidepressant-like properties of the synthetic compound 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1). To further investigate the neuromodulatory effects of SeBZF1, this study aimed to assess its therapeutic efficacy in ameliorating neurobehavioral impairments induced by sleep deprivation (SD) in mice. For this purpose, a method known as multiple platforms over water was used to induce rapid eye movement (REM) SD. Two hours after acute SD (24 h), male Swiss mice received a single treatment of SeBZF1 (5 mg/kg, intragastric route) or fluoxetine (a positive control, 20 mg/kg, intraperitoneal route). Subsequently, behavioral tests were conducted to assess spontaneous motor function (open-field test), depressive-like behavior (tail suspension test), and memory deficits (Y-maze test). Brain structures were utilized to evaluate oxidative stress markers, monoamine oxidase (MAO) and acetylcholinesterase (AChE) activities. Our findings revealed that SD animals displayed depressive-like behavior and memory impairments, which were reverted by SeBZF1 and fluoxetine treatments. SeBZF1 also reverted the increase in lipoperoxidation levels and glutathione peroxidase activity in the pre-frontal cortex in mice exposed to SD. Besides, the increase in hippocampal AChE activity induced by SD was overturned by SeBZF1. Lastly, cortical MAO-B activity was reestablished by SeBZF1 in mice that underwent SD. Based on the main findings of this study, it can be inferred that the compound SeBZF1 reverses the neurobehavioral alterations induced by sleep deprivation in male Swiss mice.


Assuntos
Benzofuranos , Privação do Sono , Animais , Masculino , Camundongos , Privação do Sono/tratamento farmacológico , Benzofuranos/farmacologia , Benzofuranos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
9.
Int J Dev Neurosci ; 84(6): 520-532, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38858858

RESUMO

Hypoxia in preterm infants is a clinical condition that has been associated with cognitive and behavioral disturbances for which treatment strategies are strongly required. Melatonin administration following brain insults has been considered a promising therapeutic strategy due to its antioxidant and anti-inflammatory effects. Not surprisingly, it has been extensively studied for preventing disturbances following brain injury. This study evaluated the effects of melatonin on developmental disturbances, memory disruption, and hippocampal cell loss induced by neonatal anoxia in rats. Neonatal Wistar rats were subjected to anoxia and subsequently treated with melatonin. Later, maturation of physical characteristics, ontogeny of reflexes, learning and memory in the Morris water maze (MWM), and estimates of the number of hippocampal neurons, were evaluated. Melatonin treatment attenuated (1) female anoxia-induced delay in superior incisor eruption, (2) female anoxia-induced vibrissae placement reflexes, and (3) male and female anoxia-induced hippocampal neuronal loss. Melatonin also promoted an increase (5) in swimming speeds in the MWM. In addition, PCA analysis showed positive associations between the acoustic startle, auditory canal open, and free fall righting parameters and negative associations between the male vehicle anoxia group and the male melatonin anoxia group. Therefore, melatonin treatment attenuates both anoxia-induced developmental deficits and hippocampal neuronal loss.


Assuntos
Animais Recém-Nascidos , Hipocampo , Aprendizagem em Labirinto , Melatonina , Ratos Wistar , Animais , Melatonina/farmacologia , Melatonina/uso terapêutico , Feminino , Hipocampo/efeitos dos fármacos , Ratos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Hipóxia/complicações , Neurônios/efeitos dos fármacos , Modelos Animais de Doenças , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico
10.
Exp Brain Res ; 242(8): 1871-1879, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38864869

RESUMO

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO2max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.


Assuntos
Envelhecimento , Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Depressão , Treinamento Intervalado de Alta Intensidade , Hipocampo , Ratos Wistar , Animais , Hipocampo/metabolismo , Ratos , Depressão/metabolismo , Depressão/terapia , Depressão/fisiopatologia , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Ansiedade/metabolismo , Ansiedade/terapia , Ansiedade/fisiopatologia , Treinamento Intervalado de Alta Intensidade/métodos , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Aprendizagem em Labirinto/fisiologia , Condicionamento Físico Animal/fisiologia , Memória Espacial/fisiologia
11.
Braz J Med Biol Res ; 57: e13437, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808889

RESUMO

Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.


Assuntos
Animais Recém-Nascidos , Cognição , Hipocampo , Sevoflurano , Sevoflurano/farmacologia , Animais , Feminino , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ratos , Cognição/efeitos dos fármacos , Fatores de Tempo , Aprendizagem em Labirinto/efeitos dos fármacos , Anestésicos Inalatórios/farmacologia , Anestésicos Inalatórios/efeitos adversos , Apoptose/efeitos dos fármacos , Fatores Sexuais , Ratos Sprague-Dawley , Éteres Metílicos/farmacologia , Western Blotting , Gasometria , Disfunção Cognitiva/induzido quimicamente
12.
J Alzheimers Dis ; 99(1): 121-143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640149

RESUMO

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.


Assuntos
Doença de Alzheimer , Encéfalo , Modelos Animais de Doenças , Memória Espacial , Compostos de Vanádio , Animais , Masculino , Administração por Inalação , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Angiopatia Amiloide Cerebral/induzido quimicamente , Angiopatia Amiloide Cerebral/patologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/patologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/patologia , Aprendizagem em Labirinto/efeitos dos fármacos , Emaranhados Neurofibrilares/efeitos dos fármacos , Emaranhados Neurofibrilares/patologia , Placa Amiloide/induzido quimicamente , Placa Amiloide/patologia , Ratos Wistar , Memória Espacial/efeitos dos fármacos , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/toxicidade
13.
Horm Behav ; 162: 105538, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38574447

RESUMO

Environmental enrichment (EE) is a paradigm that offers the animal a plethora of stimuli, including physical, cognitive, sensory, and social enrichment. Exposure to EE can modulate both anxiety responses and plasma corticosterone. In this study, our objective was to explore how chronic unpredictable stress (CUS) impacts anxiety-related behaviors in male Swiss mice raised in EE conditions. Additionally, we investigated corticosterone and adrenocorticotropic hormone (ACTH) levels to assess the involvement of the hypothalamic-pituitary-adrenal (HPA) axis in mediating these responses. Mice were housed under either EE or standard housing conditions for 21 days. Afterward, they were exposed to 11 days of CUS while still reared in their distinct housing conditions, with half of the mice receiving daily pretreatment with the vehicle and the other half receiving daily metyrapone (MET) injections, an inhibitor of steroid synthesis, 30 mins before CUS exposure. Blood samples were obtained to assess plasma corticosterone and ACTH levels. The 11-day CUS protocol induced anxiety-like phenotype and elevated ACTH levels in EE mice. Chronic MET pretreatment prevented anxiety-like behavior in the EE-CUS groups, by mechanisms involving increased plasma corticosterone levels and decreased ACTH. These results suggest a role of the HPA axis in the mechanism underlying the anxiogenic phenotype induced by CUS in EE mice and shed light on the complex interplay between environmental factors, stress, and the HPA axis in anxiety regulation.


Assuntos
Hormônio Adrenocorticotrópico , Ansiedade , Corticosterona , Meio Ambiente , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Estresse Psicológico , Animais , Masculino , Sistema Hipotálamo-Hipofisário/metabolismo , Camundongos , Sistema Hipófise-Suprarrenal/metabolismo , Estresse Psicológico/metabolismo , Hormônio Adrenocorticotrópico/sangue , Corticosterona/sangue , Metirapona/farmacologia , Comportamento Animal/fisiologia , Abrigo para Animais , Aprendizagem em Labirinto/fisiologia
14.
Int. j. morphol ; 42(2): 470-478, abr. 2024. ilus
Artigo em Inglês | LILACS | ID: biblio-1558149

RESUMO

SUMMARY: We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and p- P70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression.


Evaluamos el papel y el mecanismo del acteoside en la regulación del deterioro de la memoria inducido por estrés leve crónico impredecible (ELCI). Se utilizó ELCI para inducir depresión en ratas y el establecimiento exitoso del modelo ELCI se verificó mediante una prueba de natación forzada y una prueba de preferencia de sacarosa. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos evaluaron las funciones de la memoria. Los cambios estructurales en la corteza y el hipocampo se observaron mediante tinción con hematoxilina y eosina (HE). La tinción por inmunofluorescencia y la transferencia Western determinaron los niveles de proteína. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos mostraron que había un deterioro del rendimiento de la memoria en ratas del grupo ELCI, que mejoró con el tratamiento con acteósidos. La tinción con HE mostró que la exposición a ELCI dañó la estructura de la corteza y el hipocampo, mientras que el tratamiento con actósidos alivió los cambios estructurales. En comparación con el grupo de control, los niveles de BNDF y CREB en la corteza y el hipocampo del grupo ELCI disminuyeron significativamente. Acteoside revirtió significativamente las expresiones de estas proteínas en ratas ELCI. Mientras tanto, en comparación con el grupo control, los niveles de p-mTOR y p-P70S6K en la corteza y el hipocampo del grupo ELCI aumentaron significativamente, y estos cambios fueron revertidos significativamente ELCI por el acteoside. Sin embargo, el efecto del acteoside sobre la señalización de mTOR fue notablemente bloqueado por la rapamicina, un inhibidor específico de la señalización de mTOR. El acteoside puede atenuar el deterioro de la memoria y mejorar el daño neuronal y la plasticidad sináptica en ratas con depresión, probablemente mediante la inhibición de la vía de señalización mTOR. Acteoside puede servir como un reactivo novedoso para la prevención de la depresión.


Assuntos
Animais , Ratos , Depressão/tratamento farmacológico , Polifenóis/administração & dosagem , Glucosídeos/administração & dosagem , Transtornos da Memória/tratamento farmacológico , Estresse Psicológico/complicações , Western Blotting , Imunofluorescência , Ratos Sprague-Dawley , Aprendizagem em Labirinto , Reconhecimento Psicológico/efeitos dos fármacos , Modelos Animais de Doenças , Serina-Treonina Quinases TOR/antagonistas & inibidores , Polifenóis/uso terapêutico , Escala de Avaliação Comportamental , Inibidores de MTOR , Glucosídeos/uso terapêutico , Plasticidade Neuronal/efeitos dos fármacos , Neurônios
15.
Brain Res ; 1831: 148848, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38432261

RESUMO

Alzheimer's disease is the most common neurodegenerative disease, and its treatment is lacking. In this work, we tested Amylovis-201, a naphthalene-derived compound, as a possible therapeutic candidate for the treatment of AD. For this purpose, we performed three experiments. In the first and third experiment, animals received a bilateral administration of streptozotocin and, starting 24 h after injection, a daily dose of Amylovis-201 (orally), for 17 days or for the whole time of the experiment respectively (28 days), after which learning and memory, as well as the number of hippocampal dentate gyrus cells, were assessed. In the second experiment, healthy animals received a single dose of Amylovis-201, 10 min or 5 h after the learning section to assess whether this substance could promote specific mechanisms involved in memory trace formation. Our data show that, administration of a single dose of Amylovis-201, 10 min after the end of training, but not at 5 h, produces a prolongation in memory duration, probably because it modulates specific mechanisms involved in memory trace consolidation. Furthermore, daily administration of Amylovis-201 to animals with bilateral intracerebroventricular injection of STZ produces a reduction in the loss of the hippocampus dentate gyrus cells and an improvement in spatial memory, probably because Amylovis-201 can interact with some of the protein kinases of the insulin signaling cascade, also involved in neural plasticity, and thereby halt or reverse some of the effects of STZ. Taking to account these results, Amylovis-201 is a good candidate for the therapeutic treatment of AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Animais , Estreptozocina/farmacologia , Doenças Neurodegenerativas/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Memória Espacial , Transtornos da Memória/metabolismo , Aprendizagem em Labirinto
16.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474019

RESUMO

Alzheimer's Disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracerebroventricular (ICV) injection of low to moderate doses of streptozotocin (STZ) in adult male Wistar rats can reproduce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, knowledge regarding the molecular aspects of the ICV-STZ model is still incipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on mass spectrometry (MS). To achieve that, samples from the pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differential protein abundance, pathway, and network analysis were performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in the early stages of late-onset Alzheimer's disease (LOAD), based on differentially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further investigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.


Assuntos
Doença de Alzheimer , Ratos , Masculino , Animais , Doença de Alzheimer/metabolismo , Ratos Wistar , Estreptozocina , Proteoma , Proteômica , Modelos Animais de Doenças , Aprendizagem em Labirinto
17.
Nutrients ; 16(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38337665

RESUMO

Brain physiology and morphology are vulnerable to chronic stress, impacting cognitive performance and behavior. However, functional compounds found in food may alleviate these alterations. White quinoa (Chenopodium quinoa, Wild) seeds contain a high content of n-3 fatty acids, including alpha-linolenic acid. This study aimed to evaluate the potential neuroprotective role of a quinoa-based functional food (QFF) in rats. Prepubertal male Sprague-Dawley rats were fed with rat chow or QFF (50% rat chow + 50% dehydrated quinoa seeds) and exposed or not to restraint stress protocol (2 h/day; 15 days). Four experimental groups were used: Non-stressed (rat chow), Non-stressed + QFF, Stressed (rat chow) and Stressed + QFF. Weight gain, locomotor activity (open field), anxiety (elevated plus maze, light-dark box), spatial memory (Y-maze), and dendritic length in the hippocampus were measured in all animals. QFF intake did not influence anxiety-like behaviors, while the memory of stressed rats fed with QFF improved compared to those fed with rat chow. Additionally, QFF intake mitigated the stress-induced dendritic atrophy in pyramidal neurons located in the CA3 area of the hippocampus. The results suggest that a quinoa-supplemented diet could play a protective role in the memory of chronically stressed rats.


Assuntos
Chenopodium quinoa , Ratos , Animais , Masculino , Ratos Sprague-Dawley , Aprendizagem em Labirinto , Suplementos Nutricionais , Hipocampo/fisiologia , Estresse Psicológico/psicologia
18.
J Bioenerg Biomembr ; 56(2): 87-99, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38374292

RESUMO

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.


Assuntos
Dieta Hiperlipídica , Memória Espacial , Ratos , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Ratos Wistar , NG-Nitroarginina Metil Éster/farmacologia , NG-Nitroarginina Metil Éster/metabolismo , Peróxido de Hidrogênio/metabolismo , Aprendizagem em Labirinto , Hipocampo/metabolismo , Mitocôndrias/metabolismo
19.
J Neurochem ; 168(8): 1503-1513, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37491912

RESUMO

The nucleoside guanosine is an endogenous neuromodulator associated with neuroprotection. The roles of guanosine during aging are still not fully elucidated. Guanosine modulates SUMOylation in neurons and astrocytes in vitro, but it is not known whether guanosine can modulate SUMOylation in vivo and improve cognitive functions during aging. SUMOylation is a post-translational protein modification with potential neuroprotective roles. In this follow-up study, we investigated whether guanosine could modulate SUMOylation in vivo and behavior in young and aged mice. Young (3-month-old) and aged (24-month-old) C57BL/6 mice were treated with guanosine (8 mg/kg intraperitoneal) daily for 14 days. Starting on day 8 of treatment, the following behavioral tests were performed: open field, novel object location, Y-maze, sucrose splash test, and tail suspension test. Treatment with guanosine did not change the locomotor activity of young or aged mice in the open-field test. Treatment with guanosine improved short-term memory only for young mice but did not change the working memory of either young or aged mice, as evaluated using object recognition and the Y-maze tests, respectively. Depressive-like behaviors, such as impaired grooming evaluated through the splash test, did not change in either young or aged mice. However, young mice treated with guanosine increased their immobility time in the tail suspension test, suggesting an effect on behavioral coping strategies. Global SUMO1-ylation was significantly increased in the hippocampus of young and aged mice after 14 days of treatment with guanosine, whereas no changes were detected in the cerebral cortex of either young or aged mice. Our findings demonstrate that guanosine also targets hippocampal SUMOylation in vivo, thereby contributing to a deeper understanding of its mechanisms of action. This highlights the involvement of SUMOylation in guanosine's modulatory and neuroprotective effects.


Assuntos
Envelhecimento , Guanosina , Hipocampo , Memória de Curto Prazo , Camundongos Endogâmicos C57BL , Proteína SUMO-1 , Sumoilação , Animais , Guanosina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Envelhecimento/metabolismo , Envelhecimento/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Sumoilação/efeitos dos fármacos , Masculino , Proteína SUMO-1/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos
20.
Mol Neurobiol ; 61(5): 2631-2652, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37919602

RESUMO

This study investigated the neuroprotective effects of exendin-4 (EXE-4), an analog of the glucagon-like peptide 1 receptor (GLP-1R) on memory and on the neuronal populations that constitute the hippocampus of rats submitted to a sporadic dementia of Alzheimer's type (SDAT). Male Wistar rats received streptozotocin (STZ icv, 3 mg/kg diluted in aCFS, 5 µl/ventricle) and were treated for 21 days with EXE-4 (10 µg/kg, ip; saline as the vehicle). Four groups were formed: vehicle, EXE-4, STZ, and STZ + EXE-4. The groups were submitted to Y-Maze (YM), object recognition (ORT), and object displacement tasks (ODT) to assess learning and memory. The brains were used for immunohistochemical and immunofluorescent techniques with antibodies to NeuN, cleaved caspase-3 (CC3), PCNA, doublecortin (DCX), synaptophysin (SYP), and insulin receptor (IR). STZ worsened spatial memory in the YMT, as well as short-term (STM) and long-term (LTM) memories in the ORT and ODT, respectively. EXE-4 protected against memory impairment in STZ animals. STZ reduced mature neuron density (NeuN) and increased cell apoptosis (CC3) in the DG, CA1, and CA3. EXE-4 protected against neuronal death in all regions. EXE-4 increased PCNA+ cells in all regions of the hippocampus, and STZ attenuated this effect. STZ reduced neurogenesis in DG per se as well as synaptogenesis induced by EXE-4. EXE-4 increased immunoreactivity to IR in the CA1. From these findings, EXE-4 showed a beneficial effect on hippocampal pyramidal and granular neurons in the SDAT showing anti-apoptotic properties and promoting cell proliferation. In parallel, EXE-4 preserved the memory of SDAT rats. EXE-4 appears to enhance synapses at CA3 and DG. In conclusion, these data indicate that agonists to GLP-1R have a beneficial effect on hippocampal neurons in AD.


Assuntos
Morte Celular , Exenatida , Neurônios , Animais , Masculino , Ratos , Doença de Alzheimer/patologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Proteína Duplacortina/metabolismo , Exenatida/farmacologia , Exenatida/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Peptídeos/farmacologia , Ratos Wistar , Receptor de Insulina/metabolismo , Estreptozocina , Peçonhas/farmacologia , Peçonhas/uso terapêutico
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