New Horizons: Gonadotropin-Releasing Hormone and Cognition

Topic: Brain proteins, microglia and lab models

Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function of the hypothalamic-pituitary-gonadal axis, which controls the onset of puberty and fertility. Two recent studies suggest that, in addition to controlling reproduction, the neurons in the brain that produce GnRH are also involved in the control of postnatal brain maturation, odor discrimination, and adult cognition. This review will summarize the development and establishment of the GnRH system, with particular attention to the importance of its first postnatal activation, a phenomenon known as minipuberty, for later reproductive and nonreproductive functions. In addition, we will discuss the beneficial effects of restoring physiological (ie, pulsatile) GnRH levels on olfactory and cognitive alterations in preclinical Down syndrome and Alzheimer disease models, as well as the potential risks associated with long-term continuous (ie, nonphysiological) GnRH administration in certain disorders. Finally, this review addresses the intriguing possibility that pulsatile GnRH therapy may hold therapeutic potential for the management of some neurodevelopmental cognitive disorders and pathological aging in elderly people.

@article{prevot2023-37261390,
  author  = {Prévot, V. and Tena-Sempere, M. and Pitteloud, N.},
  title   = {{New Horizons: Gonadotropin-Releasing Hormone and Cognition}},
  journal = {The Journal of clinical endocrinology and metabolism},
  year    = {2023},
  doi     = {10.1210/clinem/dgad319},
  pmid    = {37261390},
  url     = {https://doi.org/10.1210/clinem/dgad319}
}

Key findings

• Two recent studies suggest that, in addition to controlling reproduction, the neurons in the brain that produce GnRH are also involved in the control of postnatal brain maturation, odor discrimination, and adult cognition.
• In addition, we will discuss the beneficial effects of restoring physiological (ie, pulsatile) GnRH levels on olfactory and cognitive alterations in preclinical Down syndrome and Alzheimer disease models, as well as the potential risks associated with long-term continuous (ie, nonphysiological) GnRH administration in certain disorders.

Why it matters

This review discusses evidence that pulsatile GnRH therapy improved smell and cognition in preclinical Down syndrome and Alzheimer's disease models. The findings are from animal models, and the review also notes potential risks of long-term continuous GnRH administration, so this is not yet established as a treatment for people.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1210/clinem/dgad319
• PubMed: 37261390
• Original source →
• Free full text: The Journal of Clinical Endocrinology & Metabolism →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Related

Studies in the library that share something with this one. The line above each title says what.

• shares topic tags: down, syndrome Neuronal plasticity and astrocytic reaction in Down syndrome and Alzheimer disease Journal of the neurological sciences · 1990-08-01 · usefulness score 39/100
• shares topic tags: down, syndrome Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome JAMA neurology · 2021-08-01 · usefulness score 64/100
• shares topic tags: down, syndrome Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer's disease: a cross-sectional study The Lancet. Neurology · 2021-08-01 · usefulness score 62/100
• shares topic tags: down, syndrome Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study The Lancet. Neurology · 2023-01-01 · usefulness score 60/100

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial JAMA · 2003-05-01 · usefulness score 72/100 · Treatments
• A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome Nature reviews. Neuroscience · 2015-08-05 · usefulness score 52/100 · Risk factors

Related studies in Down syndrome and Alzheimer's

• Thyroid stimulating hormone-receptor overexpression in brain of patients with Down syndrome and Alzheimer's disease Life sciences · 1999-01-01 · usefulness score 36/100
• The clinical and neurobehavioral course of Down syndrome and dementia with or without new-onset epilepsy Epilepsy & behavior : E&B · 2017-02-10 · usefulness score 46/100
• Cholinesterase inhibitors: new roles and therapeutic alternatives Pharmacological research · 2004-10-01 · usefulness score 45/100
• Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: a new avenue for a disease modifying treatment of Alzheimer's? ACS chemical neuroscience · 2012-08-28 · usefulness score 36/100
• A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase Cytogenetics and cell genetics · 2000-01-01 · usefulness score 35/100
• Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2 Genes, brain, and behavior · 2009-09-22 · usefulness score 34/100

Also tagged “down”

527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.

• Unaltered expression of Fas (CD95/APO-1), caspase-3, Bcl-2 and annexins in brains of fetal Down syndrome: evidence against increased apoptosis Journal of neural transmission. Supplementum · 2001-01-01 · usefulness score 35/100 · Down syndrome and Alzheimer's
• Symptoms of dementia among adults with Down's syndrome: a qualitative study Journal of intellectual disability research : JIDR · 2007-09-01 · usefulness score 44/100 · Digital health tools
• Concordance of Biological and Clinical Staging of Alzheimer Disease Pathology in Down Syndrome JAMA Neurology · 2026-01-12 · usefulness score 46/100 · Down syndrome and Alzheimer's

Studies sharing this one's topic tags

• Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study The Lancet. Neurology · 2024-05-01 · usefulness score 67/100 · shares: down, syndrome
• Neuronal and glial gene expression in neocortex of Down's syndrome and Alzheimer's disease Journal of neuropathology and experimental neurology · 1993-05-01 · usefulness score 37/100 · shares: down, syndrome
• Plasma neurofilament light chain: A potential prognostic biomarker of dementia in adult Down syndrome patients PloS one · 2019-04-05 · usefulness score 46/100 · shares: down, syndrome
• Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024-06-28 · usefulness score 52/100 · shares: down, syndrome
• Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome Neurology · 2024-07-29 · usefulness score 55/100 · shares: down, syndrome

Similar studies

• Epilepsy in neurodegenerative diseases 2022 · Down syndrome and Alzheimer's
• Down syndrome: A curative prospect? 2020 · Down syndrome and Alzheimer's
• Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis 2013 · Down syndrome and Alzheimer's
• Glial-neurotrophic mechanisms in Down syndrome 2001 · Down syndrome and Alzheimer's
• The brain in Down syndrome 2001 · Down syndrome and Alzheimer's
• Gonadal function in young women with Down syndrome 1999 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground New therapies for treating Down syndrome require quality of life measurement American journal of medical genetics. Part A · 2013-03-12 · usefulness score 33/100
• Newest in this subject Single-cell and spatial transcriptomics of cellular heterogeneity in Alzheimer disease Nature reviews. Neuroscience · 2026-11-06 · Peer-reviewed · usefulness score 43/100
• Newest in this subject Avoidable Mortality in Adults With Down Syndrome or With Other Intellectual Disabilities JAMA network open · 2026-11-02 · Peer-reviewed · usefulness score 76/100

See all studies in Down syndrome and Alzheimer's →