Humanin, a Mitochondrial-Derived Peptide Released by Astrocytes, Prevents Synapse Loss in Hippocampal Neurons.

Zárate SC, Traetta ME, Codagnone MG, Seilicovich A, Reinés AG

Frontiers in aging neuroscience31 May 2019Cited by 55 (Europe PMC)

PMID31214013PMCIDPMC6555273DOI10.3389/fnagi.2019.00123PepBankPUB-31214013

Summary

Astroglial cells are crucial for central nervous system (CNS) homeostasis. They undergo complex morpho-functional changes during aging and in response to hormonal milieu. Ovarian hormones positively affect different astroglia parameters, including regulation of cell morphology and release of neurotrophic and neuroprotective factors. Thus, ovarian hormone loss during menopause has profound impact in astroglial pathophysilogy and has been widely associated to the process of brain aging. Humanin (HN) is a secreted mitochondrial-encoded peptide with neuroprotective effects. It is localized in several tissues with high metabolic rate and its expression decreases with age. In the brain, humanin has been found in glial cells in physiological conditions. We previously reported that surgical menopause induces hippocampal mitochondrial dysfunction that mimics an aging phenotype. However, the effect of ovarian hormone deprivation on humanin expression in this area has not been studied. Also, whether astrocytes express and release humanin and the regulation of such processes by ovarian hormones remain elusive. Although humanin has also proven to be beneficial in ameliorating cognitive impairment induced by different insults, its putative actions on structural synaptic plasticity have not been fully addressed. In a model of surgical menopause in rats, we studied hippocampal humanin expression and localization by real-time quantitative polymerase chain reaction (RT-qPCR) and double immunohistochemistry, respectively. Humanin production and release and ovarian hormone regulation of such processes were studied in cultured astrocytes by flow cytometry and ELISA, respectively. Humanin effects on glutamate-induced structural synaptic alterations were determined in primary cultures of hippocampal neurons by immunocytochemistry. Humanin expression was lower in the hippocampus of ovariectomized rats and its immunoreactivity colocalized with astroglial markers. Chronic ovariectomy also promoted the presence of less complex astrocytes in this area. Ovarian hormones increased humanin intracellular content and release by cultured astrocytes. Humanin prevented glutamate-induced dendritic atrophy and reduction in puncta number and total puncta area for pre-synaptic marker synaptophysin in cultured hippocampal neurons. In conclusion, astroglial functional and morphological alterations induced by chronic ovariectomy resemble an aging phenotype and could affect astroglial support to neuronal function by altering synaptic connectivity and functionality. Reduced astroglial-derived humanin may represent an underlying mechanism for synaptic dysfunction and cognitive decline after menopause.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

2 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Efficacy outcome
In primary hippocampal neuron cultures, humanin prevented glutamate-induced dendritic atrophy.
In plain wordsIn cultured brain neurons, humanin prevented the loss of dendrite branching that glutamate caused.
Peptide
Humanin
Outcome
DecreaseGlutamate-induced dendritic atrophy
Study
n: not reported in source
Primary cultures of hippocampal neurons with glutamate challenge
Comparator
Glutamate without humanin
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Humanin prevented glutamate-induced dendritic atrophy and reduction in puncta number and total puncta area for pre-synaptic marker synaptophysin in cultured hippocampal neurons.
1 context sentence(design, population, supporting numbers)
Summary · context
Humanin effects on glutamate-induced structural synaptic alterations were determined in primary cultures of hippocampal neurons by immunocytochemistry.
Show in the study text Report a problemFND-3121401304
02LabIn vitro (cells)Efficacy outcome
In primary hippocampal neuron cultures, humanin prevented the glutamate-induced reduction in synaptophysin puncta number and total puncta area.
In plain wordsIn cultured brain neurons, humanin prevented the glutamate-induced loss of synapse markers.
Peptide
Humanin
Outcome
IncreaseSynaptophysin puncta number and total puncta area
Study
n: not reported in source
Primary cultures of hippocampal neurons with glutamate challenge
Comparator
Glutamate without humanin
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Humanin prevented glutamate-induced dendritic atrophy and reduction in puncta number and total puncta area for pre-synaptic marker synaptophysin in cultured hippocampal neurons.
1 context sentence(design, population, supporting numbers)
Summary · context
Humanin effects on glutamate-induced structural synaptic alterations were determined in primary cultures of hippocampal neurons by immunocytochemistry.
Show in the study text Report a problemFND-3121401305

Natural levels measured3

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

03AnimalEndogenous levelAnimal study (in vivo)Other
In a rat model of surgical menopause, humanin expression was lower in the hippocampus of ovariectomized rats.
In plain wordsIn rats with surgical menopause, the body's own humanin expression was lower in the hippocampus.
Peptide
Humanin
Outcome
DecreaseHippocampal humanin expression after ovariectomy
Study
ratn: not reported in source
Rat model of surgical menopause (ovariectomy)
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Humanin expression was lower in the hippocampus of ovariectomized rats and its immunoreactivity colocalized with astroglial markers.
1 context sentence(design, population, supporting numbers)
Summary · context
In a model of surgical menopause in rats, we studied hippocampal humanin expression and localization by real-time quantitative polymerase chain reaction (RT-qPCR) and double immunohistochemistry, respectively.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121401301
04AnimalEndogenous levelAnimal study (in vivo)Mechanism
In the rat hippocampus, humanin immunoreactivity colocalized with astroglial markers.
In plain wordsIn rats, the body's own humanin was found in the same hippocampal cells as astroglial markers.
Peptide
Humanin
Outcome
Not applicableColocalization of hippocampal humanin with astroglial markers
Study
ratn: not reported in source
Rat model of surgical menopause (ovariectomy)
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
its immunoreactivity colocalized with astroglial markers.
1 context sentence(design, population, supporting numbers)
Summary · context
In a model of surgical menopause in rats, we studied hippocampal humanin expression and localization by real-time quantitative polymerase chain reaction (RT-qPCR) and double immunohistochemistry, respectively.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121401302
05LabEndogenous levelIn vitro (cells)Mechanism
In cultured astrocytes, ovarian hormones increased intracellular humanin content and release.
In plain wordsIn cultured brain support cells, ovarian hormones raised the cells' own humanin content and release.
Peptide
Humanin
Outcome
IncreaseAstrocyte humanin content and release with ovarian hormones
Study
n: not reported in source
Cultured astrocytes
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Ovarian hormones increased humanin intracellular content and release by cultured astrocytes.
1 context sentence(design, population, supporting numbers)
Summary · context
Humanin production and release and ovarian hormone regulation of such processes were studied in cultured astrocytes by flow cytometry and ELISA, respectively.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121401303

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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