Respiratory deficits in a female rat model of Parkinson's disease.

NEW FINDINGS: What is the central question of this study? How does the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease model affect the respiratory response in female rats? What effect does ovariectomy have on that response? What is the main finding and its importance? The results suggest a protective effect of ovarian hormones in maintaining normal neuroanatomical integrity of the medullary respiratory nucleus in females. It was observed that ovariectomy alone reduced neurokinin-1 density in the pre-Bötzinger complex and Bötzinger complex, and there was an incremental effect of 6-OHDA and ovariectomy on retrotrapezoid nucleus neurons. ABSTRACT: Emerging evidence indicates that the course of Parkinson's disease (PD) includes autonomic and respiratory deficiencies in addition to the classical motor symptoms. The prevalence of PD is lower in women, and it has been hypothesized that neuroprotection by ovarian hormones can explain this difference. While male PD animal models present changes in the central respiratory control areas, as well as ventilatory parameters under normoxia and hypercapnia, little is known about sex differences regarding respiratory deficits in this disease background. This study aimed to explore the neuroanatomical and functional respiratory changes in intact and ovariectomized (OVX) female rats subjected to chemically induced PD via a bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). The respiratory parameters were evaluated by whole-body plethysmography, and the neuroanatomy was monitored using immunohistochemistry. It was found that dopaminergic neurons in the substantia nigra and neurokinin-1 receptor density in the rostral ventrolateral respiratory group, Bötzinger and pre-Bötzinger complex were reduced in the chemically induced PD animals. Additionally, reduced numbers of Phox2b neurons were only observed in the retrotrapezoid nucleus of PD-OVX rats. Concerning respiratory parameters, in OVX rats, the resting and hypercapnia-induced tidal volume (VT ) is reduced, and ventilation ( V ̇ E ${\dot V_{\rm{E}}}$ ) changes independently of 6-OHDA administration. Notably, there is a reduction in the number of retrotrapezoid nucleus Phox2b neurons and hypercapnia-induced respiratory changes in PD-OVX animals due to a 6-OHDA and OVX interaction. These results suggest a protective effect induced by ovarian hormones in neuroanatomical changes observed in a female experimental PD model.

Effects of moderate alcohol consumption on behavior and neural systems of Wistar rats.

Chronic alcohol consumption affects various neurotransmitters, especially those implicated in the transitioning to alcohol use disorders (particularly dopaminergic and CRFergic systems). Few studies have investigated moderate alcohol consumption and its harmful consequences. The objective of this work was to analyze behavioral and neurochemical (dopaminergic and CRFergic systems) alterations during chronic moderate alcohol consumption. Twelve male Wistar rats were submitted to an intermittent alcohol ingestion protocol (alcohol group) for four weeks. The control group consisted of six rats. Open Field and Elevated Plus Maze tests were used for analysis of motor and anxiety-like behaviors. Immunohistochemistry analysis was performed in dopaminergic and CRFergic systems. Animals exposed to alcohol consumed moderate doses, chronic and intermittently. Behavioral tests detected fewer fecal boli in the alcohol exposed group, and immunohistochemical analysis indicated fewer dopamine-immunoreactive cells in the ventral tegmental area, and more CRF-immunoreactive cells in the anterior cingulate cortex and dorsolateral septum in this group. Thus we concluded that Wistar rats that consumed moderate doses of alcohol voluntarily and chronically showed a discreet anxiolytic effect in behavior, and a hypodopaminergic and hyperCRFergic neurochemical condition, which together are strong inducers of alcohol consumption predisposing to the development of alcohol use disorder (AUD).

The pilocarpine model of epilepsy: what have we learned?

The systemic administration of a potent muscarinic agonist pilocarpine in rats promotes sequential behavioral and electrographic changes that can be divided into 3 distinct periods: (a) an acute period that built up progressively into a limbic status epilepticus and that lasts 24 h, (b) a silent period with a progressive normalization of EEG and behavior which varies from 4 to 44 days, and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main features of the SRSs observed during the long-term period resemble those of human complex partial seizures and recurs 2-3 times per week per animal. Therefore, the pilocarpine model of epilepsy is a valuable tool not only to study the pathogenesis of temporal lobe epilepsy in human condition, but also to evaluate potential antiepileptogenic drugs. This review concentrates on data from pilocarpine model of epilepsy.

The pilocarpine model of epilepsy: what have we learned?

The systemic administration of a potent muscarinic agonist pilocarpine in rats promotes sequential behavioral and electrographic changes that can be divided into 3 distinct periods: (a) an acute period that built up progressively into a limbic status epilepticus and that lasts 24 h, (b) a silent period with a progressive normalization of EEG and behavior which varies from 4 to 44 days, and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main features of the SRSs observed during the long-term period resemble those of human complex partial seizures and recurs 2-3 times per week per animal. Therefore, the pilocarpine model of epilepsy is a valuable tool not only to study the pathogenesis of temporal lobe epilepsy in human condition, but also to evaluate potential antiepileptogenic drugs. This review concentrates on data from pilocarpine model of epilepsy.

A administração sistêmica do potente agonista muscarínico pilocarpina em ratos promove alterações comportamentais e eletrográficas que podem ser divididas em três períodos distintos: (a) período agudo o animal evolui progressivamente para o status epilepticus, que perdura por até 24h; (b) período silencioso, caracterizado pela normalização progressiva do comportamento e do EEG e pode ter uma duração de 4 a 44 dias; período crônico, aparecimento de crises epilépticas espontâneas e recorrentes (SRSs). As características das SRSs observadas nos animas durante o período crônico são semelhantes às crises parciais complexas dos seres humanos e recorrem de 2-3 vezes por semana/animal. Além disso, o modelo de epilepsia induzido pela pilocarpina é válido não somente para se estudar a patogênese da epilepsia do lobo temporal em humanos como também para se testar a viabilidade de drogas antiepilépticas. Esse artigo de revisão aborda diversos aspectos do modelo de epilepsia induzido pela pilocarpina.