Unraveling the potential of hypothalamic deep brain stimulation for obesity: Impacts on memory, neuroplasticity and brain metabolism in the Zucker rat.
Marta Casquero-Veiga, Meritxell Llorca-Torralba, Clara Bueno-Fernandez, Diego Romero-Miguel, Nicolás Lamanna-Rama, Christine Winter, Esther Berrocoso, Juan Nacher, Manuel Desco, Mª Luisa Soto-Montenegro
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Abstract
The lateral hypothalamus (LH) plays a key role in regulating energy balance and appetite, making it a potential target for deep brain stimulation (DBS) in treatment-resistant obesity. In this study, we evaluated the short and long-term in vivo effects of continuous LH-DBS over 15 days in a genetic model of obesity: the Zucker rat. We examined changes in body weight, brain glucose metabolism (via positron emission tomography, PET), and memory performance, along with ex vivo neuroplasticity in different hippocampal layers one month post-treatment. Contrary to expectations, continuous LH-DBS did not reduce the weight gain or food intake. While stimulated rats exhibited hippocampal hypermetabolism and enhanced synaptogenesis, these changes did not translate into cognitive improvements. Interestingly, long-term memory benefits were observed in all animals that underwent surgery, regardless of whether they received stimulation. In conclusion, our results do not support continuous LH-DBS as an effective treatment to reduce body weight in cases of obesity with genetic leptin resistance. However, the hippocampal modulation induced by continuous LH-DBS shows potential for addressing cognitive impairments associated with leptin resistance. These findings suggest that alternative DBS protocols may help restore hippocampal function, warranting further investigation.
期刊介绍：
Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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