Hypothyroidism induces motor deficit via altered cerebellar HB-EGF/EGFR and autophagy.

Thyroid hormones (TH) are vital for brain functions, while TH deficiency, i.e. hypothyroidism, induces neurological impairment in children and adults. Cerebellar neuronal apoptosis and motor deficits are crucial events in hypothyroidism; however, the underlying mechanism is less-known. Using a methimazole-treated hypothyroidism rat model, we investigated cerebellar autophagy, growth factor, and apoptotic mechanisms that participate in motor functions. We first identified that methimazole up-regulated cerebellar autophagy, marked by enhanced LC3B-II, Beclin-1, ATG7, ATG5-12, p-AMPKα/AMPKα, and p62 degradation as well as reduced p-AKT/AKT, p-mTOR/mTOR, and p-ULK1/ULK1 in developing and young adult rats. We probed upstream effectors of this abnormal autophagy and detected a methimazole-induced reduction in cerebellar phospho-epidermal growth factor receptor (p-EGFR)/EGFR and heparin-binding EGF-like growth factor (HB-EGF). Here, while a thyroxine-induced TH replenishment alleviated autophagy process and restored HB-EGF/EGFR, HB-EGF treatment regulated AKT-mTOR and autophagy signaling in the cerebellum. Moreover, neurons of the rat cerebellum demonstrated this reduced HB-EGF-dependent increased autophagy in hypothyroidism. We further checked whether the above events were related to cerebellar neuronal apoptosis and motor functions. We detected that comparable to thyroxine, treatment with HB-EGF or autophagy inhibitor, 3-MA, reduced methimazole-induced decrease in Nissl staining and increase in c-Caspase-3 and TUNEL-+ve apoptotic count of cerebellar neurons. Additionally, 3-MA, HB-EGF, and thyroxine attenuated the methimazole-induced diminution in riding time on rota-rod and grip strength for the motor performance of rats. Overall, our study enlightens HB-EGF/EGFR-dependent autophagy mechanism as a key to cerebellar neuronal loss and functional impairments in developmental hypothyroidism, which may be inhibited by HB-EGF and 3-MA treatments, like thyroxine.

Yoga Therapy For Medically Unexplained Physical Symptoms.

Medically unexplained physical symptoms (MUPS) is a common, yet neglected disease with a prevalence of around 25% in primary care setting. These patients present with multiple physical and psychological symptoms, without an underlying diagnosis, hampering their functional and mental wellbeing. The management of these undiagnosed symptoms through conventional treatment has not been encouraging. Patients shuttle between different specialities, seeking a diagnosis for their symptoms, making them dissatisfied and increasing healthcare burden. Yoga, as an adjunct therapy has shown to be effective in the management of MUPS related disorders such as somatoform disorder, irritable bowel syndrome (IBS) and depression and anxiety. Thus, we suggest an integrated yoga module which might help in improving both physical and psychological variable in MUPS patients and improving their overall quality of life. Furthermore, the gap in the literature on the efficacy of yoga in improving MUPS, can be addressed by planning a randomised controlled trial based on the suggested yoga module.

A prospective study evaluating emotional disturbance in subjects undergoing defecating proctography.

AIM: To investigate the prevalence of psychiatric illness in association with functional gastrointestinal disorders using defecating proctography (DP) and validated questionnaires. METHODS: We prospectively evaluated 45 subjects referred for DP using hospital anxiety and depression scale (HADS), state trait anxiety inventory (STAI), patient health questionnaire 15-item somatic symptom severity scale (PHQ-15), validated questionnaires for sexual or physical abuse; post-traumatic stress disorder questionnaire (PTSD) and ROME-III questionnaires for gastrointestinal complaints. DP results were considered negative if levator ani function was normal, rectoceles (if any) were < 4 cm and there was no evidence of intussusception, rectal prolapse, or other anatomic abnormality demonstrated. Subjects were subsequently divided into those with structural defects seen on DP (DP positive group) and those with a normal defecography study (DP negative group). RESULTS: Forty five subjects were included in the study of which 20 subjects were classified as DP negative (44.4%). There was a striking prevalence of a history of sexual abuse in DP negative group compared to the DP positive group (n = 9, 5 respectively; P = 0.036). Further, subjects in the DP negative group scored significantly higher on the HADS anxiety (6.60 ± 1.00 vs 4.72 ± 0.40, P = 0.04) and depression scales (5.72 ± 1.00 vs 3.25 ± 0.46, P = 0.01). This correlated well with significantly higher scores on the STAI state anxiety scale (42.75 ± 3.16 vs 35.6 ± 2.00, P = 0.027), PHQ-15 questionnaire (13.15 ± 0.82 vs 10.76 ± 0.97, P = 0.038) and prevalence of PTSD (20% vs 4%, P = 0.045) among DP negative subjects. There was no difference between the groups in terms of STAI trait anxiety. CONCLUSION: The findings of this prospective study demonstrate a significantly high degree of psychiatric ailments in patients with negative findings on DP who should be appropriately screened for a history of sexual abuse and symptoms of psychosocial distress.