Neuroprotective effects of levothyroxine on cognition deficits and memory in an experimental model of Huntington's disease in rats: An electrophysiological study.

Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive deficits and motor function. Levothyroxine (L-T4) is a synthetic form of Thyroxine (T4), which can improve cognitive ability. The aim of the present study was to determine the neuroprotective effect of L-T4 administration in rats with 3-nitropropionic acid (3-NP)-induced Huntington's disease. Forty-eight Wistar male rats were divided into six groups (n = 8): Group 1 control group that received physiological saline, Group 2 and 3: which received L-T4 (30 and 100 µg/kg), Group 4: HD group that received 3-NP and Groups 5 and 6: The treatment of the HD rats with L-T4 (30 and 100 µg/kg). Spatial memory, locomotor activity, and frequency of neuronal firing were assessed. After decapitation, the Brain-Derived Neurotrophic Factor (BDNF) and Total antioxidant capacity (TAC) levels in the striatum was measured. The results showed that the indices of spatial memory (mean path length and latency time) and motor dysfunction (immobility time) significantly increased, while time spent in the goal quadrant, swimming speed, spike rate, and striatum levels of BDNF significantly decreased in the HD group compared to the control group. L-T4 treatment significantly enhanced time spent in the goal quadrant, swimming speed, motor activity (number of line crossing and rearing), spike rate and striatal BDNF level. This research showed that L-T4 prevented the disruption of motor activity and cognitive deficiencies induced by 3-NP. The beneficial effects of L-T4 may be due to an increase in the concentration of BDNF and enhancement of the spike rate in the striatum.

Levothyroxine attenuates behavioral impairment and improves oxidative stress and histological alteration 3-nitropropionic acid induced experimental Huntington's disease in rats.

Huntington's disease (HD) is a neurodegenerative disorder characterized by degeneration of the striatum; it results in oxidative stress and motor deficits. Thyroid hormones regulate oxidative metabolism. In the present study, we evaluated the effect of administration of levothyroxine (LT-4) on neurobehavioral, oxidative stress, and histological changes in a rat model of HD. Forty-eight Wistar male rats were divided into the following six groups (n = 8): Group 1 (control) received physiological saline intraperitoneally (ip). Groups 2 and 3 received L-T4,30 and L-T4100 (µg/kg, ip, respectively) daily for 7 days. Group 4 (HD) received 3-nitropropionic acid (3-NP) (25 mg/kg, ip) daily for 7 days. Groups 5 and 6 received L-T4,30 and L-T4100 (µg/kg, ip, respectively) 30 min after 3-NP (25 mg/kg, ip) injection for the same duration. On the 8th day, behavioral parameters were evaluated with the Rotarod, Narrow beam walk, and Limb withdrawal tests. Oxidative markers such as Malondialdehyde (MDA) and Glutathione (GSH) levels and Superoxide dismutase (SOD) activity, in striatum tissue were measured. Moreover, striatum tissues were analyzed by Hematoxylin-eosin staining for histological alterations. We found that 3-NP administration caused motor incoordination and induced oxidative stress increased but reduced free radical scavenging. Also, increased amounts of lipid peroxides caused striatal damage as shown by histopathological evaluation. Administration of L-T4 led to increased falling time in the Rotarod, but reduced the time taken in Narrow beam walking and Limb withdrawal test. Furthermore, L-T4 increased antioxidant activity, decreased lipid peroxidation and ameliorated 3-NP-induced degeneration in neurons.

The Effects of Iron Oxide Nanoparticles Administration on Depression Symptoms Induced by LPS in Male Wistar Rats.

INTRODUCTION: Depression is a mood disorder in which feelings of sadness, loss, anger, or frustration interfere with everyday life for one to several weeks. Several studies have shown that iron nanoparticles have neuroprotective and anti-inflammatory effects. This study aimed to evaluate anti-depressive effect of iron nanoparticles in male rats. METHODS: Depression was induced by Lipopolysaccharide (LPS) adminstration. Rats were randomly assigned into six groups (10 in each group): 1) control (sterile saline solution; 200 µL, IP); 2) LPS (LPS;100 µg/kg, IP); 3) Low dose Iron Nanoparticle (LINP) (1 mg/kg, IP); 4) High dose Iron Nanoparticle (HINP), 5 mg/kg IP); 5) LPS/LINP (LPS; 100µg/kg IP+INP 1 mg/kg IP); and 6) LPS/HINP (LPS; 100 µg/kg IP+INP 5 mg/kg IP). All injections were performed every other day. To assess the effect of iron nanoparticles on depression symptoms, rats were subjected to two behavioral tests: Forced Swim Test (FST) and Open Field Test (OFT). RESULTS: Iron nanoparticles treatment in 1 mg/kg and 5 mg/kg doses groups significantly improved depression symptoms when assessed by OFT and FST. In OFT, the number of line crossings, entrance to central square, rearing and duration of attending in central square increased after iron nanoparticles adminstration in depressed rats. Iron nanoparticles adminstration reduced immobility time confirmed by FST and OFT. Also, iron nanoparticles adminstration significantly increased duration of swimming in FST depressed rats. CONCLUSION: Our results for the first time showed potential advantageous effect of iron nanoparticles administration in attenuating depression symptoms, which was possibly mediated by modulation of neurotransmitters and anti-inflammatory effects of iron nanoparticles.