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1.
J Neurochem ; 166(5): 830-846, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37434423

RESUMO

The pathological hallmark of Parkinson's disease (PD) is the intraneuronal accumulation of misfolded alpha-synuclein (termed Lewy bodies) in dopaminergic neurons of substantia nigra par compacta (SNc). It is assumed that the α-syn pathology is induced by gastrointestinal inflammation and then transfers to the brain by the gut-brain axis. Therefore, the relationship between gastrointestinal inflammation and α-syn pathology leading to PD remains to be investigated. In our study, rotenone (ROT) oral administration induces gastrointestinal tract (GIT) inflammation in mice. In addition, we used pseudorabies virus (PRV) for tracing studies and performed behavioral testing. We observed that ROT treatments enhance macrophage activation, inflammatory mediator expression, and α-syn pathology in the GIT 6-week post-treatment (P6). Moreover, pathological α-syn was localized with IL-1R1 positive neural cells in GIT. In line with these findings, we also find pS129-α-syn signals in the dorsal motor nucleus of the vagus (DMV) and tyrosine hydroxylase in the nigral-striatum dynamically change from 3-week post-treatment (P3) to P6. Following that, pS129-α-syn was dominant in the enteric neural cell, DMV, and SNc, accompanied by microglial activation, and these phenotypes were absent in IL-1R1r/r mice. These data suggest that IL-1ß/IL-1R1-dependent inflammation of GIT can induce α-syn pathology, which then propagates to the DMV and SNc, resulting in PD.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Animais , Camundongos , alfa-Sinucleína/metabolismo , Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Trato Gastrointestinal/metabolismo , Corpos de Lewy/metabolismo , Doença de Parkinson/metabolismo
2.
Sheng Li Xue Bao ; 71(5): 732-740, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646327

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by loss of dopaminergic (DA) neurons in the dense part of the substantia nigra (SNpc). Postmortem analysis of PD patients and experimental animal studies found that microglial cell activation and increased levels of pro-inflammatory factors were common features of PD brain tissue. At the same time, the invasion and accumulation of peripheric immune cells were detected in the brain of PD patients. In this paper, peripheral inflammation across the blood-brain barrier (BBB), the misfolded α-synuclein (α-syn)-induced microglial cell activation and intracerebral inflammation in PD are summarized, providing potential therapeutic measures for delaying the onset of PD.


Assuntos
Inflamação/patologia , Doença de Parkinson/patologia , Substância Negra/patologia , Animais , Barreira Hematoencefálica , Neurônios Dopaminérgicos/patologia , Humanos , Microglia , alfa-Sinucleína
3.
Sheng Li Xue Bao ; 69(2): 146-158, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28435973

RESUMO

Acute fetal hypoxia (AFH) can elicit postnatal motor deficits and cognitive impairments. To test whether lifelong acclimatization to middle altitude (MA) hypoxia has protective effects on the impairments caused by AFH, ICR mice bred at 1 900 m altitude for 6-7 generations were evaluated under AFH. On gestation day 9 (GD 9), 13 (GD 13) or 17 (GD 17), pregnant mice received a single exposure to acute hypoxia (7% O2, 6 h). Physiological and neurodevelopmental behaviors, motor function (open field), spatial learning and memory (Morris water maze), and anxiety level (elevated plus maze) were examined in the offspring from neonate to adulthood. In the neonatal age, among all the physiological and behavioral landmarks, almost no differences were found in the hypoxia groups. In the juvenile period, no obvious impairments of motor function and anxiety level were found in the hypoxia groups. In the adult period, no obvious impairment of motor function was found in hypoxia groups; Interestingly, AFH groups' offspring showed normal or enhanced long-term spatial memory ability after AFH. These data suggest that AFH cause little abnormalities in the offspring of MA-adapted mice. To further investigate the underlying mechanisms, the neuronal numbers in behavior-related brain areas (accumbens nucleus, basal amygdala and hippocampus) were counted, and the physiological parameters of the blood were measured. The morphological data showed that no obvious neuronal necrosis was found in all hypoxia groups. In addition, blood tests showed that red blood corpuscle count, hemoglobin concentration and hematocrit levels in mice raised at MA were markedly higher in both males and females, compared with controls raised at the sea level. These data suggest that lifelong acclimatization to MA hypoxia has protective effects against development delay, motor deficits and spatial learning and memory impairments induced by AFH, and the protective effects may be due to higher hemoglobin concentration and hematocrit levels in the blood. The findings may provide a better understanding of fetal hypoxia and potential intervention treatments.


Assuntos
Aclimatação , Altitude , Transtornos Cognitivos/prevenção & controle , Hipóxia Fetal/fisiopatologia , Hipóxia , Animais , Animais Recém-Nascidos , Encéfalo , Cognição , Transtornos Cognitivos/fisiopatologia , Disfunção Cognitiva , Feminino , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/fisiopatologia , Transtornos da Memória/prevenção & controle , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Aprendizagem Espacial
4.
Am J Transl Res ; 13(3): 1471-1482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841671

RESUMO

Previous studies have indicated that the generation of newborn hippocampal neurons is impaired in the early phase of Alzheimer's disease (AD). A potential therapeutic strategy being pursued for the treatment of AD is increasing the number of newborn neurons in the adult hippocampus. Recent studies have demonstrated that ginkgo biloba extract (EGb 761) plays a neuroprotective role by preventing memory loss in many neurodegenerative diseases. However, the extent of EGb 761's protective role in the AD process is unclear. In this study, different doses of EGb 761 (0, 10, 20, and 30 mg/kg; intraperitoneal injections once every day for four months) were tested on 5×FAD mice. After consecutive 4-month injections, mice were tested in learning memory tasks, Aß, and neurogenesis in the dentate gyrus (DG) of hippocampus and morphological characteristics of neurons in DG of hippocampus. Results indicated that EGb 761 (20 and 30 mg/kg) ameliorated memory deficits. Further analysis indicated that EGb 761 can reduce the number of Aß positive signals in 5×FAD mice, increase the number of newborn neurons, and increase dendritic branching and density of dendritic spines in 5×FAD mice compared to nontreated 5×FAD mice. It was concluded that EGb 761 plays a protective role in the memory deficit of 5×FAD mice.

5.
Aging (Albany NY) ; 12(14): 14232-14243, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32706757

RESUMO

Studies indicate that mutant α-synuclein (mαSyn) is involved in the pathogenesis of Parkinson's disease (PD). The mαSyn expression leads to the loss of dopaminergic neurons in the substantia nigra (SN) and consequent motor dysfunctions. Additionally, studies found that PD was accompanied by extensive neuroinflammation of SN. However, it remains unclear as to whether microglia participate in the mαSyn pathology. This issue is addressed by using AAV-mα-Syn (A30P-A53T) to overexpress the human mαSyn in the SN in view of establishing the PD model. Subsequently, minocycline (Mino) was used to inhibit microglia activity, and an interleukin-1 receptor (IL-1R1) antagonist was used to hinder the IL-1R1 function. Finally, immunohistochemistry was used to analyze phosphorylated αSyn (Ser129) and TH-positive cells in the SN. Dopamine levels were analyzed by high performance liquid chromatography. mαSyn overexpression in the SN induced motor dysfunction, decreased striatal dopamine levels, and increased pathological αSyn 12 weeks after AAV injection. The data demonstrated that inhibiting microglial activation or hindering IL-1R1 reversed the persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system, and development of Lewy body pathology caused by human mαSyn overexpression in the SN. Additionally, these findings indicate that neuroinflammation promotes the loss of neuronal cells.


Assuntos
Neurônios Dopaminérgicos/patologia , Microglia/efeitos dos fármacos , Minociclina/farmacologia , Degeneração Neural/patologia , Substância Negra/patologia , alfa-Sinucleína/biossíntese , Animais , Comportamento Animal , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Humanos , Corpos de Lewy/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora , Mutação , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Receptores Tipo I de Interleucina-1/biossíntese , Receptores Tipo I de Interleucina-1/genética , alfa-Sinucleína/genética
6.
Brain Pathol ; 30(6): 1102-1118, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32678959

RESUMO

Olfactory dysfunction is one of the early symptoms seen in Parkinson's disease (PD). However, the mechanisms underlying olfactory pathology that impacts PD disease progression and post-mortem appearance of alpha-Synuclein (α-Syn) inclusions in and beyond olfactory bulb in PD remain unclear. It has been suggested that environmental toxins inhaled through the nose can induce inflammation in the olfactory bulb (OB), where Lewy body (LB) is the first to be found, and then, spread to related brain regions. We hypothesize that OB inflammation triggers local α-Syn pathology and promotes its spreading to cause PD. In this study, we evaluated this hypothesis by intranasal infusion of lipopolysaccharides (LPS) to induce OB inflammation in mice and examined cytokines expression and PD-like pathology. We found intranasal LPS-induced microglia activation, inflammatory cytokine expression and α-Syn overexpression and aggregation in the OB via interleukin-1ß (IL-1ß)/IL-1 receptor type I (IL-1R1) dependent signaling. In addition, an aberrant form of α-Syn, the phosphorylated serine 129 α-Syn (pS129 α-Syn), was found in the OB, substantia nigra (SN) and striatum 6 weeks after the LPS treatment. Moreover, 6 weeks after the LPS treatment, mice showed reduced SN tyrosine hydroxylase, decreased striatal dopaminergic metabolites and PD-like behaviors. These changes were blunted in IL-1R1 deficient mice. Further studies found the LPS treatment inhibited IL-1R1-dependent autophagy in the OB. These results suggest that IL-1ß/IL-1R1 signaling in OB play a vital role in the induction and propagation of aberrant α-Syn, which may ultimately trigger PD pathology.


Assuntos
Corpo Estriado/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/administração & dosagem , Bulbo Olfatório/metabolismo , Receptores de Interleucina-1/metabolismo , Substância Negra/metabolismo , alfa-Sinucleína/metabolismo , Animais , Corpo Estriado/patologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Bulbo Olfatório/patologia , Transdução de Sinais/efeitos dos fármacos , Olfato/efeitos dos fármacos , Substância Negra/patologia
7.
Aging (Albany NY) ; 12(3): 2453-2470, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019902

RESUMO

Recently, mitochondrial-nuclear interaction in aging has been widely studied. However, the nuclear genome controlled by natural mitochondrial variations that influence aging has not been comprehensively understood so far. We hypothesized that mitochondrial polymorphisms could play critical roles in the aging process, probably by regulation of the whole-transcriptome expression. Our results showed that mitochondria polymorphisms not only decreased the mitochondrial mass but also miRNA, lncRNA, mRNA, circRNA and metabolite profiles. Furthermore, most genes that are associated with mitochondria show age-related expression features (P = 3.58E-35). We also constructed a differentially expressed circRNA-lncRNA-miRNA-mRNA regulatory network and a ceRNA network affected by the mitochondrial variations. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the genes affected by the mitochondrial variation were enriched in metabolic activity. We finally constructed a multi-level regulatory network with aging which affected by the mitochondrial variation in Caenorhabditis elegans. The interactions between these genes and metabolites have great values for further aging research. In sum, our findings provide new evidence for understanding the molecular mechanisms of how mitochondria influence aging.


Assuntos
Envelhecimento/genética , Caenorhabditis elegans/genética , Ciclo-Oxigenase 1/genética , DNA Mitocondrial/genética , Longevidade/genética , Transcriptoma/genética , Animais , Regulação da Expressão Gênica , Polimorfismo Genético , RNA/genética
8.
Neurosci Bull ; 34(3): 438-448, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29247318

RESUMO

Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to study white and gray matter (GM) micro-organization and structural connectivity in the brain. Super-resolution track-density imaging (TDI) is an image reconstruction method for dMRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI (stTDI), a variation of TDI with enhanced contrast for GM structures, to reconstruct direction-encoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging (DTI) method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with stTDI, but not with DTI reconstructions from the same dMRI data. The possible mechanisms underlying the enhanced GM contrast are discussed.


Assuntos
Imagem de Tensor de Difusão/métodos , Hipocampo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tupaiidae/anatomia & histologia , Córtex Visual/diagnóstico por imagem , Animais , Mapeamento Encefálico , Masculino , Vias Neurais/diagnóstico por imagem
9.
Biomed Res Int ; 2018: 7807426, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29805976

RESUMO

Tinnitus is thought to be caused by damage to the auditory and nonauditory system due to exposure to loud noise, aging, or other etiologies. However, at present, the exact neurophysiological basis of chronic tinnitus remains unknown. To explore whether the function of the limbic system is disturbed in tinnitus, the hippocampus was selected, which plays a vital role in learning and memory. The hippocampal function was examined with a learning and memory procedure. For this purpose, sodium salicylate (NaSal) was used to create a rat animal model of tinnitus, evaluated with prepulse inhibition behavior (PPI). The acquisition and retrieval abilities of spatial memory were measured using the Morris water maze (MWM) in NaSal-treated and control animals, followed by observation of c-Fos and delta-FosB protein expression in the hippocampal field by immunohistochemistry. To further identify the neural substrate for memory change in tinnitus, neurogenesis in the subgranular zone of the dentate gyrus (DG) was compared between the NaSal group and the control group. The results showed that acquisition and retrieval of spatial memory were impaired by NaSal treatment. The expression of c-Fos and delta-FosB protein was also inhibited in NaSal-treated animals. Simultaneously, neurogenesis in the DG was also impaired in tinnitus animals. In general, our data suggest that the hippocampal system (limbic system) may play a key role in tinnitus pathology.


Assuntos
Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Salicilato de Sódio/efeitos adversos , Memória Espacial/efeitos dos fármacos , Animais , Comportamento Animal , Modelos Animais de Doenças , Hipocampo/fisiologia , Masculino , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Zumbido/induzido quimicamente
10.
Transl Neurodegener ; 7: 25, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356861

RESUMO

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease characterized by intraneuronal Lewy Body (LB) aggregates composed of misfolded alpha-synuclein (α-syn). The spread of misfolded α-syn follows a typical pattern: starting in the olfactory bulb (OB) and the gut, this pathology is followed by the progressive invasion of misfolded α-syn to the posterior part of the brain. It is unknown whether the administration of human mutant alpha-synuclein (hm-α-syn, a human mutation which occurs in familial PD) into the OB of rats would trigger similar α-syn propagation and subsequently cause pathological changes in broader brain fields associated to PD and establish an animal model of prodromal PD. METHODS: hm-α-syn was overexpressed in the OB of rats with an AAV injection. Then motor and non-motor symptoms of the SD rats were tested in different behavioral tasks following the AAV injection. In follow-up studies, pathological mechanisms of α-syn spread were explored at the histological, biochemical and micro-structure levels. RESULTS: The experimental results indicated that hm-α-syn was overexpressed in the OB 3 weeks after the AAV injection. 1) overexpression of the Hm-α-syn in the OB by the AAV injection could transfer to wider adjacent fields beyond the monosynaptic scope. 2) The number of tyrosine hydroxylase positive cells body and fibers was decreased in the substantia nigra (SN) 12 weeks after AAV injection. This was consistent with decreased levels of the DA neurotransmitter. Importantly, behavioral dysfunctions were found that included olfactory impairment after 3 weeks, motor ability impairment and decreased muscular coordination on a rotarod 6 weeks after the AAV injection.3) The morphological level studies found that the Golgi staining revealed the number of neuronal branches and synapses in the OB, prefrontal cortex (PFC), hippocampus (Hip) and striatum caudate putamen (CPU) were decreased. 4) phosphorylated α-syn, at Ser-129 (pSer129), was found to be increased in hm-α-syn injected animals in comparison to controls that overexpressed GFP alone, which was also found in the most of LB stained by the thioflavine S (ThS) in the SN field. 5) A marker of autophagy (LC3B) was increased in serval fields, which was colacolizated with a marker of apoptosis in the SN field. CONCLUSIONS: These results demonstrate that expression of exogenous mutant α-syn in the OB induces pathological changes in the sensitive brain fields by transferring pathogenic α-syn to adjacent fields. This method may be useful for establishing an animal model of prodromal PD.

11.
Brain Struct Funct ; 222(4): 1733-1751, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27624528

RESUMO

Tree shrews are small mammals now commonly classified in the order of Scandentia, but have relatively closer affinity to primates than rodents. The species has a high brain-to-body mass ratio and relatively well-differentiated neocortex, and thus has been frequently used in neuroscience research, especially for studies on vision and neurological/psychiatric diseases. The available atlases on tree shrew brain provided only limited information on white matter (WM) anatomy. In this study, diffusion tensor imaging (DTI) was used to study the WM anatomy of tree shrew, with the goal to establish an image-based WM atlas. DTI and T2-weighted anatomical images were acquired in vivo and from fixed brain samples. Deterministic tractography was used for three-dimensional reconstruction and rendering of major WM tracts. Myelin and neurofilaments staining were used to study the microstructural properties of certain WM tracts. Taking into account prior knowledge on tree shrew neuroanatomy, tractography results, and comparisons to the homologous structures in rodents and primates, an image-based WM atlas of tree shrew brain was constructed, which is available to research community upon request.


Assuntos
Encéfalo/anatomia & histologia , Tupaiidae/anatomia & histologia , Substância Branca/anatomia & histologia , Animais , Atlas como Assunto , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Masculino
13.
Neurosci Lett ; 640: 144-151, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-27984200

RESUMO

Chronic morphine administration induces neural plasticity followed by withdraw. And clinic observation indicates that obvious cognitive deficits are found during withdrawal. However, current neural substrates that regulate dysfunction in withdrawal are unknown. In our studies, chronic morphine administration was used to induce the spontaneous withdrawal model in rats. A series of cognitive abilities was tested to explore brain function. To further evaluate the neural substrates of dysfunction, Manganese-enhanced MRI(MEMRI) was used to map the dysfunctional regions in vivo.We observed that chronic morphine administration could induce obvious withdrawal behaviors in abstinence followed by cognitive impairments, such as impairments in working memory, reward, interaction and enhancement of anxiety. Our in-vivo MEMRI data using the voxel-wise comparisons showed that the manganese-enhanced signal intensity (VMI) within morphine withdrawal groups was increased in cingulate cortex (Cg), secondary motor cortex (M2), CA3 subfield of hippocampus, dorsal striatum (D-striatum), retrosplenial cortex (RS), shell subregion of NAc (AcbSh), core subregion of NAc (AcbC), central nucleus of amygdala (CeC), basolateral amygdaloid nucleus (BLA), central amygdaloid nucleus (CeM), anterior hypothalamic area, central (AHC), ventral tegmental area (VTA) and scaphoid thalamic nucleus (SC).However, decreasing of VMI was found in the ventrolateral striatum (V-striatum) and lateral posterior thalamic nucleus (LP) compared to the control group. These brain regions were beleived to be components of the memory, executive, limbic and regulatory systems. Therefore, our present studies indicate that withdrawal induced by chronic morphine adiministration could disturb brain function leading to multi-systems state shifts and cognitive deficits in abstinence.


Assuntos
Estimulantes do Sistema Nervoso Central/efeitos adversos , Transtornos Cognitivos/psicologia , Morfina/efeitos adversos , Síndrome de Abstinência a Substâncias/psicologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Mapeamento Encefálico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Emoções , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo , Ratos Sprague-Dawley , Recompensa , Comportamento Social , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/fisiopatologia
14.
Neurosci Lett ; 614: 70-6, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26655477

RESUMO

Research in the last decade demonstrated that the NMDA receptor (NMDAR) has an important role in opiate-induced neural and behavioral plasticity. In addition, increased levels of FosB-like proteins (FosB/ΔFosB) were found to be related to morphine withdrawal behaviors. However, the relationship between NMDAR and FosB/ΔFosB in sensitive brain regions during morphine withdrawal is largely unknown. In this study, we aimed to investigate NMDAR dynamics and FosB/ΔFosB levels in multiple brain regions and whether they are related in sensitive brain regions during morphine abstinence. Quantitative immunohistochemistry was adopted to test NMDAR and FosB/ΔfosB levels during morphine withdrawal in rats. Increased NMDAR and FosB/ΔFosB levels were found in the nucleus accumbens core (AcbC), nucleus accumbens shell (AcbSh), central amygdaloid nucleuscapsular part (CeC), ventral tegmental area (VTA) and cingulate cortex (Cg). Double-immunofluorescence labeling indicated that NMDAR colocalized with Fos/ΔFosB in these five regions. These results suggest that multiple phenotypic regions are mediated by NMDAR and Fos/ΔFosB during morphine withdrawal, such as the motivational (AcbC, AcbSh), limbic (CeC, VTA) and executive (Cg) system pathways, and may be the primary targets of NMDAR and Fos/ΔfosB that impact morphine withdrawal behaviors.


Assuntos
Encéfalo/efeitos dos fármacos , Morfina/efeitos adversos , Entorpecentes/efeitos adversos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Síndrome de Abstinência a Substâncias/metabolismo , Animais , Encéfalo/metabolismo , Masculino , Ratos Sprague-Dawley , Síndrome de Abstinência a Substâncias/psicologia
15.
Front Behav Neurosci ; 9: 74, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25859195

RESUMO

Many neuropsychiatric disorders, such as schizophrenia, have been associated with olfactory dysfunction and abnormalities in the prepulse inhibition (PPI) response to a startle reflex. However, whether these two abnormalities could be related is unclear. The present investigations were designed to determine whether theblockage of olfactory sensory input by zinc sulfate infusion in the olfactory naris (0.5 ml, 0.17 M, ZnE) can disturb the PPI response. Furthermore, a bilateral microinjection of lidocaine/MK801 in the olfactory bulb (OB) was administered to examine whether the blockage of olfactory sensory input could impair the PPI response. To identify the neural projection between olfaction and PPI-related areas, trans-synaptic retrograde tracing with the recombinant pseudorabies virus (PRV) was used. Our results demonstrated that blockage of olfactory sensory input could disturb olfactory behavior. In the function studies, we demonstrated that blockage of olfactory sensory input could impair the pre-pulse inhibition of the startle response following decreased c-Fos expression in relevant brain regions during the PPI responses. Furthermore, similar and more robust findings indicated that blockage of olfactory sensory input by microinjection of lidocaine/MK801 in the OB could impair the PPI response. In the circuit-level studies, we demonstrated that trans-synaptic retrograde tracing with PRV exhibited a large portion of labeled neurons in several regions of the olfactory cortices from the pedunculopontine tegmental nucleus (PPTg). Thus, these data suggest that the olfactory system participates in the PPI regulating fields and plays a role in the pre-pulse inhibition of the startle response in rats.

16.
Int J Pediatr Otorhinolaryngol ; 78(7): 995-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24814236

RESUMO

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. This study aims to investigate the pathogenesis CMV-induced hearing loss from the view of integrity of blood-labyrinth-barrier (BLB). METHODS: Newborn BALB/c mice were randomly divided into three groups (n=22, respectively): CMV group, control group and normal group. The CMV group and control group were intracerebrally injected with equal volume (15 µl) of murine CMV (MCMV; 10(4)IU/0.1 ml) and PBS, respectively, and normal group did not receive any treatment. After three weeks, auditory-evoked brainstem response was assessed, and permeability of BLB was evaluated by Evans blue method. Means between groups were compared using t-test. RESULTS: We observed that mice injected with MCMV had a hearing loss and it was connected with the permeability changes of BLB. Besides, using hematoxylin-eosin staining, we noticed hyperaemia in stria vascularis and spiral ligament and bleeding in scala vestibule and scala tympani in CMV group. CONCLUSION: All these data indicated the possible association between CMV-induced hearing loss and BLB dysfunction with the characteristics of inflammation. Our data provide a possible path to investigate the mechanism of CMV-induced hearing damage.


Assuntos
Permeabilidade Capilar , Infecções por Citomegalovirus/complicações , Orelha Interna/irrigação sanguínea , Perda Auditiva/virologia , Animais , Animais Recém-Nascidos , Audiometria , Cóclea/patologia , Corantes/farmacocinética , Azul Evans/farmacocinética , Potenciais Evocados Auditivos do Tronco Encefálico , Hemorragia/patologia , Hiperemia/patologia , Camundongos , Camundongos Endogâmicos BALB C
17.
J Neurosci Methods ; 220(1): 9-17, 2013 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-24012828

RESUMO

BACKGROUND: Tree shrews are close relatives of primates, and are increasingly used as models in the research of vision, social stress and neurological/psychiatric diseases. However, neuroimaging techniques, for example magnetic resonance (MR) imaging, are only rarely applied to this species to study the structure and function of the brain. A template MR image set, which is essential for morphometry/volumetric analysis, of tree shrew brain has been lacking in the literature. NEW METHOD: High-resolution anatomical MR images and diffusion tensor images of the brain were acquired from male Chinese tree shrews (Tupaia belangeri chinensis), and resampled to an isotropic resolution of 200 µm × 200 µm × 200 µm. Population-based image templates of tree shrew brain, including gray matter/white matter/cerebrospinal fluid probability maps and a fractional anisotropy template, were constructed at this spatial resolution, all in a reference space. Digital masks of representative anatomical structures, including hippocampus, amygdala and cingulum bundle, were created. RESULT: With the templates constructed, the volumes of bilateral hippocampus and amygdala were measured using a template-facilitated semi-automated approach to be 59.8 ± 8.3 and 64.3 ± 3.4 mm(3), respectively. COMPARISON WITH EXISTING METHOD(S): For the first time, high-resolution MR image templates of tree shrew brain were reported. The average volume of bilateral hippocampus measured with the template-facilitated semi-automated approach was found to be similar to the result obtained by the much more labor-intensive manual approach. CONCLUSIONS: The MR image templates obtained in this study are useful for analyzing neuroimage data of tree shrew brain. The templates are freely available to the scientific community upon request.


Assuntos
Anatomia Artística , Atlas como Assunto , Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética , Tupaiidae/anatomia & histologia , Animais , Imagem de Tensor de Difusão , Processamento de Imagem Assistida por Computador , Masculino
18.
Pharmacol Biochem Behav ; 103(3): 526-34, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23103203

RESUMO

Previous studies have shown that olfactory impairment by disrupting the olfactory epithelium prior to morphine administration attenuated the development addiction-related behaviors. However, it is unclear whether olfactory impairment will affect the expression of already established addiction-related behaviors. To address this issue, mice were conditioned with morphine to induce behavioral sensitization and condition placed preference (CPP). After an abstinence period, the animals were subjected to either an intranasal ZnSO(4) effusion (ZnE) or sham treatment with saline. Behavioral sensitization and CPP reinstatement were evaluated 24h later, as well as the expression of c-Fos protein, a marker of activated neural sites, in brain regions of interest. It was found that ZnE treatment attenuated morphine-induced behavioral sensitization and reinstatement of CPP. Compared to the saline-treated ones, the ZnE-treated animals showed reduced c-Fos expression in the nucleus accumbens (NAc) associated with behavioral sensitization, and in the NAc, cingulate cortex, dentate gyrus, amygdala, lateral hypothalamus and ventral tegmental area associated with CPP reinstatement. Together, these results demonstrated that acute olfactory impairment could attenuate already established addiction-related behaviors and expression of c-Fos in drug addiction related brain regions, perhaps by affecting the coordination between reward and motivational systems in the brain.


Assuntos
Comportamento Aditivo/fisiopatologia , Condicionamento Psicológico/fisiologia , Extinção Psicológica/fisiologia , Morfina/farmacologia , Mucosa Olfatória/fisiologia , Animais , Comportamento Aditivo/induzido quimicamente , Sensibilização do Sistema Nervoso Central/efeitos dos fármacos , Sensibilização do Sistema Nervoso Central/fisiologia , Condicionamento Psicológico/efeitos dos fármacos , Discriminação Psicológica/efeitos dos fármacos , Discriminação Psicológica/fisiologia , Modelos Animais de Doenças , Extinção Psicológica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Mucosa Olfatória/efeitos dos fármacos , Mucosa Olfatória/lesões , Percepção Olfatória/efeitos dos fármacos , Percepção Olfatória/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Sulfato de Zinco
19.
Dongwuxue Yanjiu ; 34(E1): E26-34, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23389984

RESUMO

Association between the reward caused by consuming drugs and the context in which they are consumed is essential in the formation of morphine-induced conditioned place preference (CPP). Glucocorticoid receptor (GRs) activation in different regions of the brain affects reward-based reinforcement and memory processing. A wide array of studies have demonstrated that blockage of GRs in some brain areas can have an effect on reward-related memory; however, to date there have been no systematic studies about the involvement of glucocorticoids (GCs) in morphine-related reward memory. Here, we used the GR antagonist RU38486 to investigate how GRs blockage affects the sensitization and CPP behavior during different phases of reward memory included acquisition, retrieval and reconsolidation. Interestingly, our results showed RU38486 has the ability to impair the acquisition, retrieval and reconsolidation of reward-based memory in CPP and sensitization behavior. But RU38486 by itself cannot induce CPP or conditioned place aversion (CPA) behavior. Our data provide a much more complete picture of the potential effects that glucocorticoids have on the reward memory of different phases and inhibit the sensitization behavior.


Assuntos
Morfina , Receptores de Glucocorticoides , Animais , Memória/efeitos dos fármacos , Camundongos , Mifepristona , Morfina/farmacologia , Ratos Sprague-Dawley , Recompensa
20.
Behav Brain Res ; 233(1): 71-8, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22569574

RESUMO

Animals attain information about their environment through different sense organs. For example, the dominant external resource about the environment for rodents is obtained through olfaction. Many environmental conditions (stress or enriched environment) are known to affect an animal's susceptibility to drug addiction. However, it is not known how external information is integrated and paired with drug stimuli to develop into addictive behavior. Here, we investigated the effects of olfactory epithelium lesions induced with ZnSO4 effusion (ZnE) on morphine-induced sensitization and conditioned place preference in mice. We found that the lesion of the olfactory epithelium attenuated the repeated morphine (40 mg/kg)-induced behavioral sensitization and morphine-induced conditioned place preference (CPP) behaviors, such as hyper-locomotion during morphine (40 mg/kg) conditioned training. Additionally, the expression of FosB-like proteins, transcription factors associated with behavioral alterations, in the nucleus accumbens of the brain was attenuated in morphine administered mice treated by ZnE. Taken together, these results indicated that lesion of the olfactory epithelium lead to a decrease in morphine sensitization and CPP behavior in mice as well as modulate specific molecular markers of neuroadaption to drugs of abuse. These findings also suggest that olfaction plays an important role in the development of addictive behaviors that can be modulated by external actions.


Assuntos
Condicionamento Operante/efeitos dos fármacos , Discriminação Psicológica/fisiologia , Morfina/farmacologia , Entorpecentes/farmacologia , Mucosa Olfatória/lesões , Mucosa Olfatória/fisiologia , Análise de Variância , Animais , Condicionamento Operante/fisiologia , Discriminação Psicológica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Odorantes , Estimulação Luminosa , Proteínas Proto-Oncogênicas c-fos/metabolismo , Fatores de Tempo , Tato/fisiologia , Sulfato de Zinco/farmacologia
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