A single injection of imipramine affected proliferation in the hippocampus of adult Swiss mice depending on the route of administration, doses, survival time and lodging conditions.

Swiss mice may be valuable for the screening of antidepressants in preclinical trials. Acute treatment with antidepressants may affect the behaviour of Swiss mice, but the effects on their hippocampal neurogenesis remain unknown. The present work aims to assess the influence of acute treatment with antidepressants on cell proliferation in the dentate gyrus of the hippocampus of adult Swiss mice. Cell proliferation was estimated by ex vivo counting of Ki-67 immunoreactive nuclei (Ki-67-ir) in the dentate gyrus of Swiss mice housed in standard or enriched environments, at survival-times 2 or 24 h after imipramine injection Independent of the experimental group, intraperitoneal imipramine (0 or 30 mg/kg) failed to change the number of Ki-67-ir in the hippocampus of mice. Through intracerebroventricular route, imipramine reduced the number of Ki-67-ir in the hippocampus of Swiss mice at the dose of 0.06 nmol and increased it at the dose 0.2 nmol. At the dose 0.2 nmol, not 0.06 nmol, imipramine increased the immunoreactivity to doublecortin (a marker for immature neurons) in the hippocampus of mice. The effects of intracerebroventricular injection of imipramine on neurogenesis markers were seen 24 h after the injection in mice housed in standard conditions. The effects of intracerebroventricular injection of imipramine on neurogenesis markers were absent in mice housed in enrichment or 2 h after the injection. These data suggest that acute treatment with imipramine may affect proliferation in the hippocampus of adult Swiss mice depending on the route of administration, doses, survival time and lodging conditions.

Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test.

Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent.

Repercussões morfológicas e funcionais do exercício sobre a regeneração nervosa periférica / Morphological and functional repercussion on peripheral nerve regeneration after exercises

INTRODUÇÃO: A indicação de exercícios físicos como abordagem terapêutica após lesões nervosas periféricas, apesar de resultados clínicos favoráveis, ainda não é consenso na literatura pertinente. Objetivos: Este estudo buscou avaliar a interferência do exercício em roda motorizada no processo de regeneração nervosa periférica. MATERIAIS E MÉTODOS: Foram utilizados 48 ratos Wistar divididos proporcionalmente em quatro grupos de 12 ratos cada (seis controles e seis experimentais). Após treinamento, os ratos foram submetidos à axonotmese do nervo ciático direito. Todos os grupos iniciaram o regime de exercícios diários 24 horas após a lesão, porém com durações diferenciadas (G1 por 28 dias; G2 por 21 dias, G3 por 14 dias e G4 por sete dias). O exercício teve tempo e velocidade ajustados de acordo com o tempo de tratamento para cada grupo. RESULTADOS: Por meio do cálculo do Índice Funcional do Ciático, os animais submetidos ao exercício apresentaram sinais de atraso na recuperação funcional da marcha, em comparação a animais controles. Na análise histológica dos nervos lesionados, observou-se que animais exercitados apresentaram sinais de preservação dos axônios no coto proximal e de degeneração no coto distal, e os animais exercitados por somente sete dias não apresentaram a mesma característica degenerativa no coto distal. A aplicação de exercícios ativos e sem carga em animais que sofreram axonotmese interfere negativamente no processo de recuperação funcional de alguns parâmetros da marcha. CONCLUSÃO: Apesar de o exercício ativo não ter interferido na manutenção da viabilidade neuronal nos sítios proximais à lesão, sua continuidade prejudicou a viabilidade dos cotos neurais distais, provável causa do atraso na recuperação funcional da marcha.

INTRODUCTION: This study aimed to investigate if exercise in motorized wheel can affect the process of peripheral nerve regeneration in a rat model of axonotmesis. MATERIAL AND METHODS: Forty-eight Wistar rats were divided equally into four groups containing six experimental and six control subjects. After proper training, the rats underwent right sciatic nerve axonotmesis. All groups started the exercises, in a daily basis, 24 hours after nerve injury, but at different durations (28 days for G1, 21 days for G2, 14 days for G3 and seven days for G4). Both duration and speed of the exercises were gradually adjusted during the experiments. RESULTS: The Sciatic Function Index revealed that exercised animals showed clear signs of delayed functional gait recovery. The histological analysis of injured nerves revealed that exercised animals showed signs of proximal stump preservation and degenerative signs in the distal stump. In other hand, exercised animals during seven days only showed axonal preservation in the distal stump. CONCLUSION: Based on these results, we believe that active exercises should be avoided, at least during the peripheral nerve regeneration process, i.e., during first 21 days after axonotmesis.".

Investigação dos efeitos do exercício terapêutico sobre a regeneração nervosa periférica / Investigation of therapeutic exercise effects on peripheral nerve regeneration

O sistema nervoso periférico apresenta relativa capacidade de rege-neração após uma lesão. Após a axonotmese o nervo ciático produzrespostas morfo-funcionais, no músculo alvo, no epicentro da lesão ealguns distritos neuronais retrógrados. Apesar dos avanços terapêuti-cos, a restauração funcional é incompleta na maioria dos casos. Nestecontexto, nós testamos se o exercício (nado) é capaz de interferir namarcha funcional e reações de plasticidade nos motoneurônios damedula espinhal. Quarenta ratos foram divididos em quatro grupos(n=10 cada), submetidos a 30 min/dia de nado, iniciando no 1, 7, 14,21 dias após lesão do nervo ciático. Todos os grupos apresentaramrecuperação funcional, não observamos diferenças significantes nosnúmeros de motoneurônios da medula espinhal entre os diferentesgrupos estudados. De acordo com a análise funcional e histológica, oexercício terapêutico, nas condições do presente estudo, foi incapazde acelerar o processo regenerativo.

The peripheral nervous system exhibits a remarkable ability to regenerateafter injury. The sciatic nerve reactions following axonotmesis produce morpho-functional responses at the target muscle, injury epicenter and at certain retrograde neuronal districts. Despite therapeutic advancements,the functional restoration is incomplete in most cases. In this context, we tested if exercise (swimming) is able to interfere in both functional gait recovery and plastic reactions in the motoneurons of the spinal cord. FortyWistar rats were divided into four groups (n=10 each), submitted to a 30 min/day swimming routine, beginning 1, 7, 14 or 21 days after the sciatic nerve injury. All groups exhibited functional recovery, significant differences were not observed in the number of spinal motoneurons among the groups studied. According to both functional and histological analysis, therapeutic exercise, in the conditions of the present study, was unable to accelerate the regeneration process.