European Journal of Biomedical and Pharmaceutical Sciences

NUTRITIONAL SUPPLEMENTS CO-ENZYMEQ10 AND OMEGA3 FATTY-ACID CO-ADMINISTRATION RELIEVES NEUTRITIC PLAQUE, DYSKINESIA AND APOPTOSIS IN HALOPERIDOL INDUCED DOPAMINE DEPLETION IN MICE

*Oyeleke Abiodun Abioye, Onaolapo Adejoke Yetunde and Onaolapo Olakunle James

ABSTRACT

Introduction: Dopamine is crucial in executive functions and motor system control. Its depletion appears to be the patho-physiological hallmark of several neurodegenerative diseases including but not limited to Parkinson’s, schizophrenia, addiction and attention deficit disorders. This study examined the effects of Co-enzyme Q10 (CQ10) and omega-3 fatty acid co-supplementation in haloperidol induced dopamine depletion in mice. Materials and Method: Adult male mice weighing 30-35g each were grouped into six (A-F) of 10animals each. Group A control, fed standard diet, Group B, ip haloperidol (HAL) while groups C, oral Levodopa Cabidopa (LD), D and E, CQ1O diet (120 mg/kg of feed) and omega-3 fatty acid (500 mg/kg of feed) diet respectively, following ip haloperidol. Group F co-administered CQ10 and omega-3 fatty acid diet with ip haloperidol. All administrations were daily and lasted 28 days. Behaviours of mice in the open field apparatus, radial arm maze and anxiety related elevated plus maze were assessed, following which animals were sacrificed. Prefrontal cortex sections were homogenized for malondialdehyde (MDA), Interleukin -10 (IL-10), caspase-3 and dopamine and also processed for histological and immunohistochemical studies. Results: Result showed a significant [F (9, 90) = 21.9, p < 0.001] decrease in locomotor activity with HAL, HAL&LD and a significant increase with HAL&CQ10&Ώ-3F compared to control. An increase in radial arm maze spatial working memory with HAL&CQ10, HAL&Ώ-3 and a decrease with HAL and HAL&LD compared to control. Compared to HAL&LD, there was an increase in open arm with HAL&CQ10, HAL&Ώ-3F and HAL&CQ10&Ώ-3F and a decrease in closed arm with HAL&Ώ-3F and HAL&CQ10&Ώ-3F. Lipid peroxidation measured as MDA concentration [F (9, 90) = 22.10, p < 0.001] increased significantly with HAL, HAL&LD, and decreased with HAL&CQ10, HAL&Ώ-3F, HAL&CQ10&Ώ-3F compared to control. Compared to HAL&LD, there was an increase in the IL-10levels with HAL&CQ10, HAL&Ώ-3F and HAL&CQ10&Ώ-3F respectively. Compared to HAL, dopamine increases significantly with HAL&LD, HAL&CQ10, HAL&Ώ-3F and HAL&CQ10&Ώ-3F. Compared to HAL&LD, there was a decrease in the Caspase-3activity with HAL&CQ10and HAL&CQ10&Ώ-3F respectively. Normal pyramidal cells with normal cytoplasmic distribution of nissl bodies were seen in HAL&CQ10&Ώ-3F, while groups HAL and HAL&LD showed comparatively reduced staining intensities with poor distribution of nissl bodies within their cytoplasm. Bielschowsky silver staining revealed neuritic plaques and argyrophilic structures in the HAL treated group. These fibrillary amyloid deposits were absent in the supplemented groups. Neuron Specific Enolase immunoreactivity is present HAL and HAL&LD while absent in HAL&CQ10and HAL&CQ10&Ώ-3F. Nil astrocytic reaction to dopamine depletion also seen in the prefrontal cortex of HAL&Ώ-3F, HAL&CQ10 and HAL&CQ10&Ώ-3F. Conclusion: The study concluded that CQ10 and omega3 fatty acid co-supplementation ameliorates neuroinflammation, lipid peroxidation, neutritic plaque and apoptosis in haloperidol induced dopamine depletion in mice.

Keywords: Dopamine depletion; Neuroinflammation; CoQ10; Omega3 fatty- acid.