RESUMO
OBJECTIVE: The cerebellum is a key structure involved in coordinated motor planning, cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities. MATERIALS AND METHODS: In this experimental study, slow administration of quinolinic acid (QA, 5 µl of 200 µmol, 1 µl/minute) in the right cerebellar hemisphere (lobule VI) caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student's t test. RESULTS: The QA treated group showed marked motor learning deficits on the rotating rod test (p=0.0001), locomotor asymmetry on the cylinder test (p=0.0001), dysmetria on the beam balance test (p=0.0001), abnormalities in neuromuscular strength on the hang wire test (p=0.0001), spatial memory deficits in the Morris water maze (MWM, p=0.001) and fear conditioned memory on the passive avoidance test (p=0.01) over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p=0.001) and granular cell density (p=0.0001) in the lesioned hemisphere of the cerebellum. CONCLUSION: Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies.
RESUMO
Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and the range of interests and activities. However, neuronal processing studies have suggested that hyper-perception, hyper-attention, and enhanced memory, which may lie at the heart of most autistic symptoms. Pregnant Wistar rats were administered by either Valproic Acid (VPA, 500mg/kg) or Phosphate Buffer Saline (PBS) during fetal neural tube development on embryonic day 12.5. All offspring were subjected to various tests. The present study examined social interaction, repetitive behaviors, nociception and tactile threshold, anxiety as well as spatial memory. Histological analyses of cells in five regions of the hippocampus were done to determine neuronal density in both groups. A single intra-peritoneal injection of VPA to pregnant rats produced severe autistic-like symptoms in the offspring. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions, enhanced stereotyped, repetitive behaviors, increased nociception threshold and anxiety at postnatal day (PND) 30 and PND 60. The Morris water maze learning paradigm revealed enhanced spatial memory at PND 60. Furthermore, histological analysis showed that the neuronal density in five separate regions of hippocampus (CA1, CA2, CA3, Dentate gyrus and Subiculum) were increased at PND 67. This work suggests that early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological and neuroanatomical hypotheses. This study provides further evidence to support the notion that spatial memory and hippocampal cell density are increased in this animal model of autism.
