Mood alterations, anxiety, and cognitive impairments associated with adult-onset hypothyroidism often persist despite replacement treatment. In rodent models of hypothyroidism, replacement does not bring 3-iodothyronamine (TAM) brain levels back to normal. TAM is a thyroid hormone derivative with cognitive effects. Using a pharmacological hypothyroid mouse model, we investigated whether augmenting levothyroxine (L-T) with TAM improves behavioural correlates of depression, anxiety, and memory and has an effect on hippocampal neurogenesis. Hypothyroid mice showed impaired performance in the novel object recognition test as compared to euthyroid mice (discrimination index (DI): 0.02 ± 0.09 vs. 0.29 ± 0.06; t = 2.515, = 0.02). L-T and L-T+TAM rescued memory (DI: 0.27 ± 0.08 and 0.34 ± 0.08, respectively), while TAM had no effect (DI: -0.01 ± 0.10). Hypothyroidism reduced the number of neuroprogenitors in hippocampal neurogenic niches by 20%. L-T rescued the number of neuroprogenitors (mean diff = 106.9 ± 21.40, t = 4.99, p = 0.003), while L-T+TAM produced a 30.61% rebound relative to euthyroid state (mean diff = 141.6 ± 31.91, t = 4.44, p = 0.004). We performed qPCR analysis of 88 genes involved in neurotrophic signalling pathways and found an effect of treatment on the expression of , , , , , , and . Our data confirm that L-T is necessary and sufficient for recovering memory and hippocampal neurogenesis deficits associated with hypothyroidism, while we found no evidence to support the role of non-canonical TH signalling.
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http://dx.doi.org/10.3390/ijms241813845 | DOI Listing |
Stem Cell Res Ther
December 2024
Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Background: The hippocampus is associated with mood disorders, and the activation of quiescent neurogenesis has been linked to anxiolytic effects. Near-infrared (NIR) light has shown potential to improve learning and memory in human and animal models. Despite the vast amount of information regarding the effect of visible light, there is a significant gap in our understanding regarding the response of neural stem cells (NSCs) to NIR stimulation, particularly in anxiety-like behavior.
View Article and Find Full Text PDFStem Cell Reports
December 2024
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China; Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China. Electronic address:
Adult hippocampal neurogenesis (AHN), the process of generating new neurons from adult neural stem/progenitor cells (NSPCs), is crucial for cognitive functions and is influenced by numerous factors, including metabolic processes. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme in glycolysis, catalyzes the production of pyruvate, which undergoes either oxidative phosphorylation or anaerobic oxidation. We observed that PKM2 is highly expressed in NSPCs, but its significance remains unclear for AHN and cognition.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
November 2024
Longhua Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200032, China.
Depression, a heterogeneous disorder with symptoms involving emotion, cognition, and behavior, is characterized by high morbidity, low treatment acceptance, and recurrent episodes. It is expected to become a major disease in the global healthcare burden by 2030. The pathogenesis of depression is complex, involving genetic, environmental, neurological, immune, endocrine and other factors, among which neuroplasticity plays a key role in the development of depression and antidepressant treatment.
View Article and Find Full Text PDFIntroduction: This study aimed to explore the impact and mechanism of Scutellariae radix (SR), dried root of Scutellaria baicalensis Georgi of Labiatae, on prenatal stress (PS) induced anxiety-like and depression-like behavior in the offspring in a mouse prenatal stress model.
Methods: The open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were utilized to assess the behavior of the offspring. Histological changes were evaluated using HE staining and Nissl staining.
Curr Protoc
December 2024
Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, College of Medicine, Bryan, Texas.
Neuronal injury, neurodegeneration, and neuroanatomical changes are key pathological features of various neurological disorders, including epilepsy, stroke, traumatic brain injury, Parkinson's disease, autism, and Alzheimer's disease. Accurate quantification of neurons and interneurons in different brain regions is critical for understanding the progression of neurodegenerative disorders in animal models. Traditional scoring methods are often superficial, biased, and unreliable for evaluating neuropathology.
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