Exploring the Pharmacognostical and Phytochemical Profiles of Aqueous Extracts of Kalanchoe.

The use of plants for medicinal purposes has a long history, however it is desirable a continuous evaluation seeking for complementary scientific evidences for their safe application. Species within the Kalanchoe genus are often referred to as "miracle leaf" due to their remarkable healing properties. Traditionally, these plants have been used to treat infections, inflammation, and cancer. Despite their widespread use, the identification of their active components remains incomplete. This study aimed to differentiate K. crenata (KC), K. marmorata (KM), and K. pinnata (KP) by conducting detailed histochemical and phytochemical analyses, and to assess their antioxidant capabilities. The investigation revealed significant differences between the species, highlighting the variability in phenolic (PC) and flavonoid contents (FC) and their distinct antioxidant effects. The KM demonstrated the greatest results (PC: 59.26±1.53 mgEqGA/g; FC: 12.63±0.91 mgEqCQ/g; DPPH⋅ (IC50): 110.66 ug/mL; ABTS⋅+ (IC50): 26.81 ug/mL; ORAC: 9.65±0.75 mmolTE) when compared to KC and KP. These findings underscore a new reference for research within the Kalanchoe genus.

Exploring Parkinson's Disease-Associated Depression: Role of Inflammation on the Noradrenergic and Serotonergic Pathways.

Parkinson's disease (PD) is a multifactorial disease, with genetic and environmental factors contributing to the disease onset. Classically, PD is a movement disorder characterized by the loss of dopaminergic neurons in the nigrostriatal pathway and intraneuronal aggregates mainly constituted of the protein α-synuclein. However, PD patients also display non-motor symptoms, including depression, which have been linked to functional abnormalities of non-dopaminergic neurons, including serotonergic and noradrenergic ones. Thus, through this comprehensive literature review, we shed light on the noradrenergic and serotonergic impairment linked to depression in PD, focusing on the putative involvement of inflammatory mechanisms.

The new Ribopeaks (RPK-II): Updated and enlarged tool for bacterial classification based on r-protein m/z data.

Ribopeaks is a rapid, sensitive, and economic web tool for bacterial identification based on m/z data from MALDI-TOF MS. To provide greater accuracy and robustness in the Ribopeaks analyzes we present an updated bacterial identification tool version, called Ribopeaks II (RPK-II). RPK-II contains a larger database, with r-protein data from fully sequenced bacterial genomes and optimized algorithms. Furthermore, this new version provides additional information about the identified bacterium, regarding antibiotic resistance.

Cymbopogon citratus (DC.) Stapf, citral and geraniol exhibit anticonvulsant and neuroprotective effects in pentylenetetrazole-induced seizures in zebrafish.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC.) Stapf (C. citratus) is consumed as an infusion in folk medicine due to its pharmacological properties and action in the central nervous system. Epilepsy is a neurological disorder that affects millions of people. Since the currently available antiepileptic drugs often cause undesirable side effects, new alternative therapeutic strategies based on medicinal plants have been proposed. AIM OF THE STUDY: This study aimed to investigate the anticonvulsant and neuroprotective effects of C. citratus essential oil (EO) and hydroalcoholic extract (E1) from its leaves, as well as of its related compounds citral (CIT) and geraniol (GER) against the effects of pentylenetetrazole (PTZ) induced seizures in zebrafish (Danio rerio). MATERIALS AND METHODS: To evaluate the anticonvulsant properties of the samples, adult animals were pre-treated (by immersion) and subsequently exposed to PTZ solution. The involvement of GABAA receptors in the antiepileptic effects was investigated by the coadministration of flumazenil (FMZ), a known GABAA receptor antagonist. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) were assessed in zebrafish brain homogenates after PTZ exposure. RESULTS: All samples increased the latency time for the first seizure, which was reduced when animals were pretreated with FMZ, suggesting the involvement of GABAA receptors in the observed properties. The association between CIT and GER at the lowest concentration studied showed a synergistic effect on the anticonvulsant activity. Decreases in MDA and NO levels and increases in GSH and CAT levels in the brain of treated animals suggested the neuroprotective effect of the compounds investigated. CONCLUSIONS: Our results proved that C. citratus EO, E1, CIT and GER have anticonvulsant effects in zebrafish and could be used as a promising adjuvant therapeutic strategy for epilepsy treatment. Furthermore, zebrafish demonstrated to be an alternative animal model of epilepsy to evaluate the anticonvulsant and neuroprotective effects of C. citratus.

Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson's disease.

The most common features of Parkinson's disease (PD) are motor impairments, but many patients also present depression and memory impairment. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to be effective in patients with treatment-resistant major depression. Thus, the present study evaluated the action of ketamine on memory impairment and depressive-like behavior in an animal model of PD. Male Wistar rats received a bilateral infusion of 6 µg/side 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). Short-term memory was evaluated by the social recognition test, and depressive-like behaviors were evaluated by the sucrose preference and forced swimming tests (FST). Drug treatments included vehicle (i.p., once a week); ketamine (5, 10 and 15 mg/kg, i.p., once a week); and imipramine (20 mg/kg, i.p., daily). The treatments were administered 21 days after the SNc lesion and lasted for 28 days. The SNc lesion impaired short-term social memory, and all ketamine doses reversed the memory impairment and anhedonia (reduction of sucrose preference) induced by 6-OHDA. In the FST, 6-OHDA increased immobility, and all doses of ketamine and imipramine reversed this effect. The anti-immobility effect of ketamine was associated with an increase in swimming but not in climbing, suggesting a serotonergic effect. Ketamine and imipramine did not reverse the 6-OHDA-induced reduction in tyrosine hydroxylase immunohistochemistry in the SNc. In conclusion, ketamine reversed depressive-like behaviors and short-term memory impairment in rats with SNc bilateral lesions, indicating a promising profile for its use in PD patients.

Anxiolytic properties of Cymbopogon citratus (DC.) stapf extract, essential oil and its constituents in zebrafish (Danio rerio).

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC.) Stapf (Poaceae) leaves is often consumed as infusion in folk medicine due to its therapeutic properties. This plant is also rich in essential oil, which has several beneficial effects to the human health. It is known that medications commonly used to treat anxiety disorders cause undesirable side effects. Thus, it is important to evaluate the anxiolytic effects of natural products from plants, such as C. citratus, as an alternative therapy to treat these disorders. OBJECTIVE: The aim of this study was to investigate the anxiolytic properties of C. citratus essential oil (EO), hydroalcoholic extract (E1), citral (CIT), geraniol (GER) and the mixture of these terpenoids, as well as its possible mechanism of action by using zebrafish as an anxiety model. METHODS: Adult zebrafish were treated (by immersion) with C. citratus EO, E1, CIT and/or GER. The anxiolytic effects were analyzed by using the light-dark test. The mechanism involved in the anxiolytic effects was further investigated by the coadministration of flumazenil (FMZ), an antagonist of GABAA receptors. The total polyphenols (phenolic and flavonoid compounds) content of E1 was determined by using spectrophotometric assays. RESULTS: All analyzed samples showed a remarkable anxiolytic effect on zebrafish in the highest concentrations, as the animals showed a preference for the light side of the tank. Furthermore, the observed effect of EO, E1, CIT and GER was reversed by pre-treatment with FMZ, suggesting that GABAergic receptors were involved in the anxiolytic effect displayed by these samples. The association between CIT and GER in the lowest studied concentrations showed an interesting synergistic behavior on anxiolytic effect observed in light-dark test. Besides, it was demonstrated that E1 was constituted by phenolic and flavonoid compounds, which could be involved in the observed effect. CONCLUSION: This work has proved that the low-cost zebrafish can be an adequate alternative as an animal model to evaluate the anxiolytic effect of C. citratus and its related compounds. Moreover, the involvement of GABAA receptors could be responsible for the effect showed by the samples. These obtained results can potentially validate the ethnopharmacological use of C. citratus as a medicinal plant for the treatment of anxiety disorders in folk medicine.

Effects of ketamine on vocal impairment, gait changes, and anhedonia induced by bilateral 6-OHDA infusion into the substantia nigra pars compacta in rats: Therapeutic implications for Parkinson's disease.

Parkinson's disease is a chronic neurodegenerative disorder characterized by cardinal motor features, such as bradykinesia, but also vocal deficits (e.g. difficulties to articulate words and to keep the tone of voice) and depression. In the present study, rats with bilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta were evaluated for changes in the emission of 50-kHz ultrasonic vocalizations, gait impairment (catwalk test), and depressive-like behaviour (sucrose preference test). Furthermore, we evaluated the effect of repeated treatment (28 days) with ketamine (5, 10, and 15 mg/kg, ip, once per week) or imipramine (15 mg/kg, ip, daily). The lesion had prominent effects on the production of 50-kHz ultrasonic vocalizations (reduced call numbers, call durations, total calling time, and increased latency to start calling), led to gait impairment (increased run duration and stand of right forelimb) and induced anhedonia (reduced sucrose preference). Also, significant correlations between gait changes, sucrose preference, and ultrasonic calling were found, yet, except for run duration and sucrose preference, these correlations were low indicating that these associations are weak. Importantly, ketamine and imipramine reversed lesion-induced anhedonia and improved gait impairments, but neither drug improved ultrasonic calling. In conclusion, the substantia nigra lesion with 6-hydroxydopamine induced subtle motor and non-motor manifestations, reflecting key features of the wide clinical spectrum of early Parkinson's disease. Furthermore, the present results suggest a potential efficacy of ketamine on depression and gait alterations in Parkinson's disease.

A Simple and High-yield Synthesis of Hexadecyl Ferulate and Its In Vitro Antioxidant Potential

ABSTRACT Ferulic acid (FA) is a phenolic compound with well-known antioxidant potential that can be used as a promising anti-inflammatory and anti-cancer molecule. Furthermore, it has been reported to have neuroprotective activity. One of the main problems, which limit its clinical use, is its low bioavailability when administered orally. This limitation can be circumvented by changes in their structure and/or for preparing lipid-based formulations. The aim of this study was to synthesize a derivative of FA, the hexadecyl ferulate (HF). This compound would be more susceptible to pass through blood-brain barrier (BBB) due to its lipophilic character. The HF was obtained by Steglich esterification and yielded 76.77 ± 1.35%. Its structural characterization was performed by spectroscopic methods of Fourier-transformed infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). FTIR spectrum of HF presented two typical bands of ester group, a C=O ester stretching band at 1725 cm-1 and a C-O stretching band at 1159 cm-1. The 1H and 13C spectral data confirmed the chemical structure of HF. Regarding the 13C NMR spectrum, HF showed a chemical shift at δ 167.39 ppm which corresponded to the carbonyl carbon of the ester group. Concerning the in vitro antioxidant potential, HF had equivalent or improved scavenger activity than FA leading to IC50 values of 0.083 ± 0.009 nmol.mL-1 and 0.027 ± 0.002 nmol.mL-1 in DPPH radical scavenging and ABTS radical cation decolorization assays, respectively. Further studies are required in order to investigate the antioxidant effect of HF in biological media.

Depression in Parkinson's Disease: The Contribution from Animal Studies.

Besides being better known for causing motor impairments, Parkinson's disease (PD) can also cause many nonmotor symptoms, like depression and anxiety, which can cause significant loss of life quality and may not respond to regular drugs treatment. In this review, we discuss the depression in PD, based on data from studies in humans and rodents. Depression frequency seems higher in PD patients than in general population, despite high variation in data due to diagnosis disparities. Development of depression in PD seems more likely to be caused by the nigrostriatal pathway degeneration than as a consequence of the awareness of disease prognostic, and it seems to be related to dopaminergic, noradrenergic, and serotoninergic synapses deficits. The dopaminergic role could be more significant, since it can modulate the release of the others, and its depletion is progressive, due to the degenerative feature of PD. Highly regarded in major depression, serotonin can be depleted in rats after nigrostriatal damage, but data from human patients are more conflicting. Animal studies can help in understanding the neurobiological mechanisms of depression in PD and the pursuit for more effective drugs for its treatment, but they lack the complexity of the disease progression, especially the nondopaminergic degeneration.

Abnormal Cerebrovascular Reactivity in Patients with Parkinson's Disease.

Background. Orthostatic hypotension (OH) is an important nonmotor manifestation of Parkinson's disease (PD). Changes in cerebrovascular reactivity may contribute to this manifestation and can be monitored using transcranial Doppler. Objective. To identify possible changes in cerebrovascular reactivity in patients with OH. Methods. Twenty-two individuals were selected and divided into three groups: with and without OH and controls. Transcranial Doppler was used to assess basal mean blood flow velocity, postapnea mean blood flow velocity, percentage increase in mean blood flow velocity, and cerebrovascular reactivity as measured by the breath-holding index. Results. PD patients had lower values of basal velocity (p = 0.019), postapnea velocity (p = 0.0015), percentage increase in velocity (p = 0.039), and breath-holding index (p = 0.04) than the controls. Patients with OH had higher values of basal velocity (p = 0.09) and postapnea velocity (p = 0.19) but lower values of percentage increase in velocity (p = 0.22) and breath-holding index (p = 0.32) than patients without OH. Conclusions. PD patients present with abnormalities in a compensatory mechanism that regulates cerebral blood flow. OH could be an indicator of these abnormalities.

Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.

A Doença de Parkinson é uma doença neurodegenerativa relacionada à idade, caracterizada pela morte lenta e progressiva de neurônios dopaminérgicos da substância negra pars compacta. O Hypericum perforatum (H. perforatum) é um fitoterápico utilizado como antidepressivo, apresentando propriedades antioxidantes, anti-inflamatórias e nootrópicas. Neste trabalho, avaliaram-se os efeitos do tratamento com H. perforatum no comportamento rotatório de ratos no modelo da doença de Parkinson induzido pela administração unilateral de 6-OHDA no feixe prosencefálico medial. Ratos Wistar machos foram tratados com H. perforatum (100, 200 ou 400 mg/kg, v.o.) por 35 dias (do 28º dia antes até o 7º dia após a lesão). As rotações ipsilaterais e contralaterais à lesão foram registradas no 7º, 14º e 21º dias após a cirurgia. As três doses de H. perforatum utilizadas reduziram o número de rotações contralaterais, indicando um possível efeito neuroprotetor da planta. Porém, o H. perforatum não impediu a redução na expressão da enzima tirosina hidroxilase no estriado lesionado, quantificada por Western blot. Propomos que o H. perforatum possa bloquear o aumento da expressão dos receptores dopaminérgicos no estriado lesionado com 6-OHDA. Entretanto, estudos adicionais são necessários para identificar o mecanismo exato pelo qual o H. perforatum reduziu o número de rotações contralaterais. Os resultados do presente estudo sugerem o H. perforatum como um potencial agente terapêutico para a doença de Parkinson.

Both the dorsal hippocampus and the dorsolateral striatum are needed for rat navigation in the Morris water maze.

The multiple memory systems theory proposes that the hippocampus and the dorsolateral striatum are the core structures of the spatial/relational and stimulus-response (S-R) memory systems, respectively. This theory is supported by double dissociation studies showing that the spatial and cue (S-R) versions of the Morris water maze are impaired by lesions in the dorsal hippocampus and dorsal striatum, respectively. In the present study we further investigated whether adult male Wistar rats bearing double and bilateral electrolytic lesions in the dorsal hippocampus and dorsolateral striatum were as impaired as rats bearing single lesions in just one of these structures in learning both versions of the water maze. Such a prediction, based on the multiple memory systems theory, was not confirmed. Compared to the controls, the animals with double lesions exhibited no improvement at all in the spatial version and learned the cued version very slowly. These results suggest that, instead of independent systems competing for holding control over navigational behaviour, the hippocampus and dorsal striatum both play critical roles in navigation based on spatial or cue-based strategies.

Roles of D1-like dopamine receptors in the nucleus accumbens and dorsolateral striatum in conditioned avoidance responses.

RATIONALE: Aversively motivated learning is more poorly understood than appetitively motivated learning in many aspects, including the role of dopamine receptors in different regions of the striatum. OBJECTIVES: The present study investigated the roles of the D1-like DA receptors in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) on learning and performance of conditioned avoidance responses (CARs). METHODS: Adult male Wistar rats received intraperitoneal (i.p.), intra-NAc, or intra-DLS injections of the D1 dopamine receptor agonist SKF 81297 or the D1 receptor antagonist SCH 23390 20 min before or immediately after a training session in the CAR task two-way active avoidance, carried out 24 h before a test session. RESULTS: Pre-training administration of SCH 23390, but not SKF 81297, caused a significant decrease in the number of CARs in the test, but not in the training session, when injected into the DLS, or in either session when injected into the NAc. It also caused a significant increase in the number of escape failures in the training session when injected into the NAc. Systemic administration caused a combination of these effects. Post-training administrations of these drugs caused no significant effect. CONCLUSIONS: The results suggest that the D1-like receptors in the NAc and DLS play important, though different, roles in learning and performance of CAR.

Microdialysis study of striatal dopamine in MPTP-hemilesioned rats challenged with apomorphine and amphetamine.

Motor impairments of Parkinson's disease (PD) appear only after the loss of more than 70% of the DAergic neurons of the substantia nigra pars compacta (SNc). An earlier phase of this disease can be modeled in rats that received a unilateral infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) into the SNc. Though these animals do not present gross motor impairments, they rotate towards the lesioned side when challenged with DAergic drugs, like amphetamine and apomorphine. The present study aimed to test whether these effects occur because the drugs disrupt compensatory mechanisms that keep extracellular levels of dopamine in the striatum (DA(E)) unchanged. This hypothesis was tested by an in vivo microdialysis study in awake rats with two probes implanted in the right and left striatum. Undrugged rats did not present turning behaviour and their basal DA(E) did not differ between the lesioned and sham-lesioned sides. However, after apomorphine treatment, DA(E) decreased in both sides, but to a larger extent in the lesioned side at the time the animals started ipsiversive turning behaviour. After amphetamine challenge, DA(E) increased in both sides, becoming significantly higher in the non-lesioned side at the time the animals started ipsiversive turning behaviour. These results are in agreement with the hypothesis that absence of gross motor impairments in this rat model of early phase PD depends on maintenance of extracellular DA by mechanisms that may be disrupted by events demanding its alteration to higher or lower levels.

Learning processing in the basal ganglia: a mosaic of broken mirrors.

In the present review we propose a model to explain the role of the basal ganglia in sensorimotor and cognitive functions based on a growing body of behavioural, anatomical, physiological, and neurochemical evidence accumulated over the last decades. This model proposes that the body and its surrounding environment are represented in the striatum in a fragmented and repeated way, like a mosaic consisting of the fragmented images of broken mirrors. Each fragment forms a functional unit representing articulated parts of the body with motion properties, objects of the environment which the subject can approach or manipulate, and locations the subject can move to. These units integrate the sensory properties and movements related to them. The repeated and widespread distribution of such units amplifies the combinatorial power of the associations among them. These associations depend on the phasic release of dopamine in the striatum triggered by the saliency of stimuli and will be reinforced by the rewarding consequences of the actions related to them. Dopamine permits synaptic plasticity in the corticostriatal synapses. The striatal units encoding the same stimulus/action send convergent projections to the internal segment of the globus pallidus (GPi) and to the substantia nigra pars reticulata (SNr) that stimulate or hold the action through a thalamus-frontal cortex pathway. According to this model, this is how the basal ganglia select actions based on environmental stimuli and store adaptive associations as nondeclarative memories such as motor skills, habits, and memories formed by Pavlovian and instrumental conditioning.

Non-motor function of the midbrain dopaminergic neurons.

The roles of the nigrostriatal pathway are far beyond the simple control of motor functions. The tonic release of dopamine in the dorsal and ventral striatum controls the choice of proper actions toward a given environmental situation. In the striatum, a specific action is triggered by a specific stimulus associated with it. When the subject faces a novel and salient stimulus, the phasic release of dopamine allows synaptic plasticity in the cortico-striatal synapses. Neurons of different regions of cortical areas make synapses that converge to the same medium spine neurons of the striatum. The convergent associations form functional units encoding body parts, objects, locations, and symbolic representations of the subject's world. Such units emerge in the striatum in a repetitive manner, like a mosaic of broken mirrors. The phasic release of dopamine allows the association of units to encode an action of the subject directed to an object or location with the outcome of this action. Reinforced stimulus-action-outcome associations will affect future decision making when the same stimulus (object, location, idea) is presented to the subject in the future. In the absence of a minimal amount of striatal dopamine, no action is initiated as seen in Parkinson's disease subjects. The abnormal and improper association of these units leads to the initiation of unpurposeful and sometimes repetitive actions, as those observed in dyskinetic patients. The association of an excessive reinforcement of some actions, like drug consumption, leads to drug addiction. Improper associations of ideas and unpleasant outcomes may be related to traumatic and depressive symptoms common in many diseases, including Parkinson's disease. The same can be said about the learning and memory impairments observed in demented and nondemented Parkinson's disease patients.

Facilitation of short-term social memory by ethanol in rats is mediated by dopaminergic receptors.

Ethanol is a drug that has apparently opposite effects on memory processes depending on when it is given relative to the task, as well as the nature of the task under study. Recently, we demonstrated that acute low doses of ethanol (0.5 and 1.0 g/kg, i.p.) improve the short-term social memory in rats in a specific and time-dependent manner, and that this action is, at least in part, related to opioid, but not to muscarinic receptors. In the present study, we evaluated whether this positive effect of ethanol on the short-term memory of rats is related to a reducing impact of interference during the task through two different procedures: the introduction of an unfamiliar juvenile rat or the placing of the adult rat in the open field during the inter-exposure interval. The actions of reserpine (0.4 and 0.8 mg/kg, s.c.), haloperidol (0.05 and 0.2 mg/kg, i.p.), the D2 receptor antagonist sulpiride (20.0 and 50.0 mg/kg, i.p.) and the D1 receptor antagonist SCH 23390 (0.01 and 0.03 mg/kg, s.c.) and their interaction with ethanol (1.0 g/kg, i.p.) in relation to short-term memory were also studied. The administration of ethanol (1.0 g/kg, i.p.), immediately after the end of the first presentation, did not reduce the effect on social memory of the introduction of an unfamiliar juvenile or placing the adult rat in the open field during the inter-exposure interval. The facilitatory effect of ethanol on social memory was inhibited by the pretreatment with reserpine and it was antagonized by the administration of haloperidol or sulpiride, but not by SCH 23390. These results indicate that the facilitation of short-term social memory by ethanol is not related to a reduction in the deleterious impact of interference and that this action of ethanol is mediated, at least in part, by D2 receptors, but not by D1 dopaminergic receptors.

Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats.

The present study investigated the effects of intranigral MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) infusion on rats treated with phosphatidylserine and evaluated in two memory tasks and on striatal dopamine levels. The results indicated that MPTP produced a significant decrease in the avoidance number in comparison to sham-operated and non-operated rats submitted to a two-way avoidance task. MPTP-lesioned rats exhibited an increase in the latencies to find the platform in cued version of the water maze in comparison to sham-operated and non-operated animals. The tested toxin reduced striatal dopamine levels in comparison to sham-operated and non-operated groups. A final surprising result was that phosphatidylserine was unable to reverse the cognitive deficits produced by MPTP or the reduction of striatal dopamine levels. In conclusion, the data suggest that MPTP is a good model to study the early impairment associated with Parkinson's disease and phosphatidylserine did not improve the memory impairment induced by MPTP.

Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system.

The aim of the present study was to test if the nigrostriatal pathway is an essential component for a water maze cued task learning and if it works independently of the hippocampal memory system. This hypothesis was tested using an animal model of Parkinson's disease in which male Wistar rats were lesioned in the substantia nigra pars compacta (SNc) by the intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), thus causing a partial depletion of striatal dopamine. SNc-lesioned and sham-operated animals were implanted bilaterally with guide cannulae above the dorsal hippocampus in order to be tested after the administration of 0.4 microl 2% lidocaine or saline into this structure. The animals were tested in a spatial or in a cued version of the water maze, memory tasks previously reported to model hippocampal-dependent spatial/relational and striatal-dependent S-R learning, respectively. Hippocampal inactivation, but not SNc lesion, impaired learning and memory in the spatial version of the water maze. An opposite situation was observed with the cued version. No significant interaction was observed between the SNc lesion and hippocampal inactivation conditions affecting scores in the spatial or in the cued version of the water maze. These results suggest that the nigrostriatal pathway is an essential part of the memory system that processes S-R learning and that it works independently of the hippocampal memory system that processes spatial/relational memories.

Impaired learning in a spatial working memory version and in a cued version of the water maze in rats with MPTP-induced mesencephalic dopaminergic lesions.

A lesion in the substantia nigra pars compacta (SNc) of rats induced by intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused specific loss of dopamine and its nonconjugated metabolites in the dorsal striatum and in the prefrontal cortex (PFC), but not in the hippocampus or the ventral striatum (nucleus accumbens). This lesion did not alter the motor performance of the rats or learning of a spatial reference memory task in the water maze but impaired learning of a spatial working memory task and also of a cued version of the water maze. The results are discussed by relating the selective memory deficits observed in these water maze tasks to the PFC, dorsal striatum, and hippocampus. Some parallels between the memory deficits in these SNc-lesioned rats and Parkinson's disease patients are also discussed.