Abstract Ammonia is involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy. Few is known about the effects of gestational exposition to ammonia in the developing brain, and the possible long-term consequences of such exposure. We aimed to evaluate the effects of ammonia exposure during the gestation and the possible long-term cognitive alterations on pups. Eight female rats were divided into two groups: (1) control (saline solution); (2) ammonia (ammonium acetate, 2,5mmol/Kg). Each rat received a single subcutaneous injection during all gestational period. The brains from 1-day-old rats were obtained to the determination of thiobarbituric acid reactive species (TBARS), protein carbonyl and nitrite/nitrate levels. Some animals were followed 30 days after delivery and were subjected to the step-down inhibitory avoidance task. It was observed a significant increase in protein carbonyl, but not TBARS or nitrite/nitrate levels, in pups exposed to ammonia. Rats exposed to ammonia presented long-term cognitive impairment. Gestational exposition to ammonia induces protein oxidative damage in the neonatal rat brain, and long-term cognitive impairment.

RESUMONovos estudos sugerem que os ácidos graxos poliinsaturados, como o ômega-3, podem reduzir os sintomas da esquizofrenia. O presente estudo avaliou o efeito preventivo do ômega-3 sobre os níveis de interleucinas (IL) e o fator neurotrófico derivado do cérebro (BDNF) em cérebros de ratos jovens submetidos a um modelo de esquizofrenia. O tratamento foi feito por 21 dias, iniciando no 30º dia de vida dos animais. Depois de 14 dias de tratamento com ômega-3 ou veículo, um tratamento concomitante com salina ou ketamina (25 mg/kg) foi iniciado e mantido até o último dia do experimento. No cortex pré-frontal dos ratos, os níveis de BDNF diminuíram em 1 h e 24 h depois da última administração de ketamina enquanto que o grupo administrado com ketamina e ômega-3 mostrou uma diminuição nos níveis de BDNF somente após as 24 h. Em contraste, ambas as intervenções induziram respostas similares quanto aos níveis de IL-1β e IL6. Esses achados sugerem que a similaridade nos níveis de IL-1β e IL6 em nossos grupos de experimento é devida ao mecanismo de ação da ketamina sobre o sistema imune. Mais estudos são necessários para explicar essa patologia. Em conclusão, de acordo com estudos prévios e considerando o atual estudo, nós sugerimos que o ômega-3 tem um papel profilático no desenvolvimento de sintomas associados à esquizofrenia.

ABSTRACTNew studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The present study evaluated the preventive effect of omega-3 on interleukines (IL) and neurotrophin brain-derived neurotrophic factor (BDNF) levels in the brains of young rats subjected to a model of schizophrenia. Treatment was performed over 21 days, starting on the 30th day of rat's life. After 14 days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25 mg/kg) was started and maintained until the last day of the experiment. BDNF levels in the rat's prefrontal cortex were decreased at 1 h and 24 h after the last administration of ketamine, whereas the group administered with ketamine and omega-3 showed a decrease in BDNF levels only after 24 h. In contrast, both interventions induced similar responses in levels of IL-1β and IL6. These findings suggest that the similarity of IL-1β and IL6 levels in our experimental groups is due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, according to previous studies and considering the current study, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.