Neuroprotective and Immunomodulatory Effects of Probiotics in a Rat Model of Parkinson's Disease.

It is now well recognized that a bidirectional relationship between gut microbiota and the brain, referred to as the gut-brain axis, plays a prominent role in maintaining homeostasis and that a disruption in this axis can result in neuroinflammatory response and neurological disorders such as Parkinson's disease (PD). The protective action of probiotics such as Bifidobacterium animalis ssp. lactis Bb12 and Lactobacillus rhamnosus GG in various animal models of PD has been reported.

Chronic Treatment with the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium lactis BB12 Attenuates Motor Impairment, Striatal Microglial Activation, and Dopaminergic Loss in Rats with 6-Hydroxydopamine-induced Hemiparkinsonism.

Gut dysbiosis is considered a risk factor for Parkinson's disease (PD), and chronic treatment with probiotics could prevent it. Here we report the assessment of a probiotic mixture [Lacticaseibacillus rhamnosus GG (LGG), and Bifidobacterium animalis lactis BB-12 (BB-12)] administered to male rats 2 weeks before and 3 weeks after injecting 6-hydroxydopamine (6-OHDA) into the right striatum, a model that mimics the early stages of PD. Before and after lesion, animals were subjected to behavioral tests: narrow beam, cylinder test, and apomorphine (APO)-induced rotations.

Developmental light deprivation transiently reduces the expression of vGluT2 and GluN2B in the rat ventral suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) is the most important circadian clock in mammals. The SCN synchronizes to environmental light via the retinohypothalamic tract (RHT), which is an axon cluster derived from melanopsin-expressing intrinsic photosensitive retinal ganglion cells. Investigations on the development of the nonimage-forming pathway and the RHT are scarce.

GABA Neurotransmission of the Suprachiasmatic Nucleus Is Modified During Rat Postnatal Development.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the brain structure that controls circadian rhythms in mammals. The SCN is formed by two neuroanatomical regions: the ventral and dorsal. Gamma-aminobutyric acid (GABA) neurotransmission is important for the regulation of circadian rhythms.

Light stimulation during postnatal development is not determinant for glutamatergic neurotransmission from the retinohypothalamic tract to the suprachiasmatic nucleus in rats.

The hypothalamic suprachiasmatic nucleus (SCN) is the leading circadian pacemaker in mammals, which synchronizes with environmental light through the retinohypothalamic tract (RHT). Although the SCN regulates circadian rhythms before birth, postnatal synaptic changes are needed for the RHT-SCN pathway to achieve total functional development. However, it is unknown whether visual experience affects developmental maturation.

Chronic feeding with 3% dried raw blueberries (V. corymbosum) reduces apomorphine-induced rotations and striatal dopaminergic loss in hemiparkinsonian rats.

Blueberries (BB) are rich in antioxidant polyphenols, and their intake could prevent Parkinson's disease (PD). Here we assessed whether rats chronically fed dried raw BB develop resistance to dopaminergic denervation and motor disorders caused by unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), a dopaminergic neurotoxin acting mainly by inducing oxidative stress. Male rats were fed either with LabDiet® alone or supplemented with 3% lyophilized raw BB for 2 weeks before and 3 weeks after injecting 6-OHDA (day 0) or vehicle (mock lesion) into the right striatum.

Synergistic antidepressant-like effect of capsaicin and citalopram reduces the side effects of citalopram on anxiety and working memory in rats.

Rationale: We have previously shown that in rats, capsaicin (Cap) has antidepressant-like properties when assessed using the forced swimming test (FST) and that a sub-threshold dose of amitriptyline potentiates the effects of Cap. However, synergistic antidepressant-like effects of the joint administration of Cap and the selective serotonin reuptake inhibitor citalopram (Cit) have not been reported.

Objectives: To assess whether combined administration of Cap and Cit has synergistic effects in the FST and to determine whether this combination prevents the side effects of Cit.

Citalopram reduces glutamatergic synaptic transmission in the auditory cortex via activation of 5-HT1A receptors.

Serotonin modulates cognitive processes and is related to various psychiatric disorders, including major depression. Administration of citalopram reduces the amplitude of auditory evoked potentials in depressed people and animal models, suggesting that 5-HT has an inhibitory role. Here, we characterize the modulation of excitatory post-synaptic currents by application of either 5-HT or agonists of 5-HT1A and 5-HT2 receptors, or by endogenous 5-HT evoked by citalopram on pyramidal neurons from layer II/III of rat auditory cortex.

Capsaicin produces antidepressant-like effects in the forced swimming test and enhances the response of a sub-effective dose of amitriptyline in rats.

Transient receptor potential vanilloid 1 (TRPV1) channels have been implicated in depression and anxiety. The aim of this study was to evaluate the antidepressant-like properties of the TRPV1 agonist capsaicin using the forced swimming test (FST) in rats. Capsaicin (0.

An automated Y-maze based on a reduced instruction set computer (RISC) microcontroller for the assessment of continuous spontaneous alternation in rats.

Continuous spontaneous alternation behavior (SAB) in a Y-maze is used for evaluating working memory in rodents. Here, the design of an automated Y-maze equipped with three infrared optocouplers per arm, and commanded by a reduced instruction set computer (RISC) microcontroller is described. The software was devised for recording only true entries and exits to the arms.

Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson's disease.

Background: The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) influences nigral dopaminergic neurons via autocrine and paracrine mechanisms. The reduction of BDNF expression in Parkinson's disease substantia nigra (SN) might contribute to the death of dopaminergic neurons because inhibiting BDNF expression in the SN causes parkinsonism in the rat. This study aimed to demonstrate that increasing BDNF expression in dopaminergic neurons of rats with one week of 6-hydroxydopamine lesion recovers from parkinsonism.

β-Adrenergic blockade protects BALB/c mice against infection with a small inoculum of Leishmania mexicana mexicana (LV4).

In order to test the influence of the sympathetic nervous system on Leishmania mexicana infection, groups of female BALB/c mice were treated (i.p.) with the non-selective β-adrenergic receptor (β-AR) antagonist (S)-propranolol (5mg/kg thrice a day), the β2-AR agonist clenbuterol (1mg/kg once a day) or the α2-AR antagonist yohimbine (2mg/kg twice a day) during 5days.

The potency and efficacy of anticholinergics to inhibit haloperidol-induced catalepsy in rats correlates with their rank order of affinities for the muscarinic receptor subtypes.

Extrapyramidal syndromes (EPS) caused by antipsychotic therapy are currently treated with anticholinergics that lack selectivity for the five muscarinic receptor subtypes. Since these receptors are heterogeneously expressed among the different classes of striatal neurons and their afferents, it can be expected that their simultaneous blockade will cause distinct, sometimes opposed, effects within the striatal circuitry. In order to test the hypothesis that the differential blockade of the muscarinic receptor subtypes would influence their potency and efficacy to prevent EPS, here we tested four anticholinergics with varying order of affinities for the muscarinic receptor subtypes, and compared their dose-response curves to inhibit haloperidol-induced catalepsy in male rats.

Clinical doses of citalopram or reboxetine differentially modulate passive and active behaviors of female Wistar rats with high or low immobility time in the forced swimming test.

The sensitivity of immobility time (IT) to antidepressant-drugs differs in rats expressing high or low motor activity during the forced swimming test (FST). However, whether this heterogeneity is expressed after the administration of the most selective serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively) is unknown. We compared the influence of either the SSRI citalopram or the SNRI reboxetine with the tricyclic antidepressant amitriptyline on two subgroups of female Wistar rats expressing high IT (HI; at or above the mean value) or low IT (LI; below the mean) during the initial 5 min of the first session of the FST.

Caffeine has greater potency and efficacy than theophylline to reverse the motor impairment caused by chronic but not acute interruption of striatal dopaminergic transmission in rats.

In order to assess whether caffeine and theophylline have the same potency and efficacy to reverse the impairment of motor function caused by acute or chronic interruption of striatal dopamine transmission, a comparison of their dose-response relationship was made in the acute model of haloperidol-induced catalepsy, and the chronic model of unilateral lesion of the dopamine nigrostriatal pathway with 6-hydroxydopamine. At equimolar doses, both drugs reduced catalepsy intensity and increased its onset latency in a dose-dependent fashion, showing comparable potencies and attaining the maximal effect at similar doses. Catalepsy intensity: caffeine ED₅₀ = 24.

A system for automatic recording and analysis of motor activity in rats.

We describe the design and evaluation of an electronic system for the automatic recording of motor activity in rats. The device continually locates the position of a rat inside a transparent acrylic cube (50 cm/side) with infrared sensors arranged on its walls so as to correspond to the x-, y-, and z-axes. The system is governed by two microcontrollers.

Quinolinic acid lesions of the pedunculopontine nucleus impair sleep architecture, but not locomotion, exploration, emotionality or working memory in the rat.

Anatomical and functional studies have shown that the NADPH-diaphorase-positive cholinergic neurons of the pedunculopontine nucleus (PPN) send projections to several areas in the brain. The purpose of this work was to investigate whether bilateral lesions with quinolinic acid, a neurotoxin with greater selectivity for NADPH-diaphorase-positive neurons, aimed at the compact portion of the PPN would affect the performance of adaptive behaviors, such as sleep, locomotion, and spontaneous alternation. Lesioned animals were divided in a low lesion group (LL, <50% neuron loss) and a high lesion group (HL, ≥50% neuron loss).

Treatment of Parkinson's disease: nanostructured sol-gel silica-dopamine reservoirs for controlled drug release in the central nervous system.

Introduction: We have evaluated the use of silica-dopamine reservoirs synthesized by the sol-gel approach with the aim of using them in the treatment of Parkinson's disease, specifically as a device for the controlled release of dopamine in the striatum. Theoretical calculations illustrate that dopamine is expected to assume a planar structure and exhibit weak interactions with the silica surface.

Methods: Several samples were prepared by varying the wt% of dopamine added during the hydrolysis of tetraethyl orthosilicate.

Synergism of theophylline and anticholinergics to inhibit haloperidol-induced catalepsy: a potential treatment for extrapyramidal syndromes.

Extrapyramidal syndromes (EPS) impose a heavy burden on patients receiving antipsychotic therapy. Anticholinergics are the drugs of choice for preventing EPS, but they also produce many adverse reactions. Using the EPS model of haloperidol-induced catalepsy we evaluated the potential therapeutic value of a mixture of low doses of the non-selective adenosine antagonist theophylline (0.

[Caffeine as a preventive drug for Parkinson's disease: epidemiologic evidence and experimental support].

Introduction And Development: Prospective epidemiologic studies performed in large cohorts of men (total: 374,003 subjects) agree in which the risk of suffering Parkinson's disease diminishes progressively as the consumption of coffee and other caffeinated beverages increases. In the case of women (total: 345,184 subjects) the protective effect of caffeine is only observed in menopausal women which do not receive estrogen replacement therapy. Studies with models of acute parkinsonism in rodents have shown that caffeine reduces the loss of nigrostriatal dopaminergic neurons induced with the neurotoxins 6-hidroxidopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, effect that seems to be mediated through blockade of A(2A) adenosine receptors.

Long-lasting resistance to haloperidol-induced catalepsy in male rats chronically treated with caffeine.

Chronic caffeine consumption has been inversely associated with the risk of developing Parkinson's disease. Here we assessed whether chronic caffeine treatment increases the resistance of male Wistar rats to haloperidol (1mg/kg, s.c.

A digital programmable telemetric system for recording extracellular action potentials.

This article describes the design and preliminary evaluation of a small-sized and low energy consumption wearable wireless telemetry system for the recording of extracellular neuronal activity, with the possibility of selecting one of four channels. The system comprises four radio frequency (RF) transceivers, three microcontrollers, and a digital amplifier and filter. This constitutes an innovative distributed processing approach.

Differential effects of caffeine on the antidepressant-like effect of amitriptyline in female rat subpopulations with low and high immobility in the forced swimming test.

The interaction of caffeine (1 mg/kg) and amitriptyline (15 mg/kg) on the immobility time (IT) during Porsolt's forced swimming test (FST) was investigated in female Wistar rats. Akaike's Information Criterion indicated that the ITs recorded from 142 rats during the first day of the FST followed a bimodal distribution. Hence, the median (125.

Sustained improvement of motor function in hemiparkinsonian rats chronically treated with low doses of caffeine or trihexyphenidyl.

The effects of chronic oral treatment with low doses of caffeine (1-3 mg/kg) and trihexyphenidyl (0.1-0.2 mg/kg) were tested on hemiparkinsonian rats, which received the following treatments in a counterbalanced order: vehicle, caffeine, trihexyphenidyl, and caffeine plus trihexyphenidyl.

A novel automated rat catalepsy bar test system based on a RISC microcontroller.

Catalepsy tests performed in rodents treated with drugs that interfere with dopaminergic transmission have been widely used for the screening of drugs with therapeutic potential in the treatment of Parkinson's disease. The basic method for measuring catalepsy intensity is the "standard" bar test. We present here an easy to use microcontroller-based automatic system for recording bar test experiments.