Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study.

BACKGROUND AND AIM: Neurodegeneration has been associated with the use of combination antiretroviral therapy (cART). This study is aimed at determining if any constituent of cART can induce cerebellar limb dysmetria and spatial memory impairments. MATERIALS AND METHODS: Forty adult male Wistar rats were randomly grouped into four (n = 10): control (distilled water 0.5 mL); Tenofovir (6 mg/kg); Lamivudine (6 mg/kg) and Efavirenz (12 mg/kg). The following neurobehavioral studies were conducted: open field, beam walk, and Morris water maze. Immunohistochemistry of CD 68 and GFAP were used to test for neuroinflammation and neurodegeneration. RESULTS: There was marked increase in pyknotic pyramidal cells of the hippocampus and ghost Purkinje cells in the cerebellum of treatment groups. There was also a significant increase in oxidative stress in lamivudine and efavirenz groups. In addition, Lamivudine caused a significant increase of microglial and astrocytic activity (p < 0.001, 0.05 respectively) compared to control. The open field test showed a significant decrease (p < 0.0001) of the line crossing performance in the efavirenz, lamivudine and tenofovir (with means: 26.4, 4.6, 17.4 respectively) compared to control (50.6). There was also a significant decrease in the grooming (p < 0.05) and rearing (p < 0.01) in lamivudine group. Whereas, walk latency increased in efavirenz (p < 0.01), and lamivudine (p < 0.0001) compared to control. While hind limb slips significantly increased in efavirenz (p < 0.05) and lamivudine (p < 0.0001) compared with control group. Likewise, Lamivudine and Tenofovir exposed groups experienced a significant delay in the time to identify the hidden platform in compared to control (p < 0.05). CONCLUSION: Lamivudine altered efferent stimuli along the cerebellospinal tracts thereby causing motor impairments. The degenerating Purkinje fibers may have induced marked neurodegeneration in the hippocampus resulting in impaired spatial memory.

Testicular histomorphometry and semen quality of adult Wistar rats following juvenile oral lead intoxication

Empirical evidence has shown that childhood lead (Pb) intoxication impairs cognitive function and heightens the risk of dementia in young adult humans. However, the effects of juvenile Pb toxicity on testicular morphometry and semen quality in young adulthood require further studies. Using a rodent model, juvenile (4 weeks old) Wistar rats were randomized to receive either normal saline or lead acetate in their drinking water at 0.5% (5000 ppm), 1.5% (15000 ppm) and 2.5% (25000 ppm) for 7 weeks. At 11 weeks postnatal, young adult rats were anaesthetized and their cauda epididymides excised for sperm analysis. The left testicles were homogenized in phosphate buffer and the supernatants assayed for testosterone by the enzyme immunoassay technique. The right testicles were processed for photomicroscopy by the haematoxylin and eosin technique. Using ImageJ software, testicular sections were subjected to morphometric analysis. Our findings showed that juvenile Pb intoxication alters testicular histomorphometry in young adulthood as indicated by significant (P<0.05) reductions in seminiferous tubule diameters and lumen, and marked attenuation of the germinal epithelium in the Pb-exposed rats compared with the non-exposed age-matched controls. Furthermore, findings from sperm analysis showed significantly low sperm density and motility following oral Pb exposure, while the percentage of deformed and dead sperm cells had increased significantly (P<0.05). Meanwhile, testicular interstitial compartment and the associated Leydig cells were unperturbed, and testicular testosterone levels were not significantly different between the control and Pb-treated groups (P>0.05). These findings show that Pb intoxication initiated prior to pubescence alters testicular histomorphometry and lowers semen quality in young adult Wistar rats, and these changes were unconnected with testicular testosterone levels

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