Medical Studies on Pregnenolone – Neuropsychiatric Disorders
Pregnenolone has been shown to exert positive effects on the brain. For example, it improves memory and learning, helps maintain a healthy mood and supports the modulation of cognitive functions.
Memory Support at Any Age
Numerous studies over the past three decades have shown that even low-dose pregnenolone supplementation helps to support memory – long-term memory in particular. In addition, pregnenolone protects the body from age-related cognitive problems while promoting nervous system health. Incidentally, healthy younger people who are frequently exposed to stressful situations can also benefit from this function of pregnenolone, as this substance supports optimal mental performance by preventing neuronal damage.
Sub-optimal pregnenolone levels have been associated with mood disorders, cognitive decline, anxiety and panic attacks, schizophrenia or dementia, psychosis and cannabinoid-related dysfunctions. Studies have attributed some of the beneficial effects of pregnenolone to the direct effect of pregnenolone, while other effects can be attributed to substances metabolized from pregnenolone, such as DHEA, progesterone and their derivatives. Of particular interest is the fact that pregnenolone can promote neurogenesis; a property that can be especially useful in neurodegenerative diseases.
Medical Studies on Pregnenolone – Immune System
The Neuroactive Steroid Pregnanolone Glutamate: Anticonvulsant Effect, Metabolites and Its Effect on Neurosteroid Levels in Developing Rat Brains
Pregnanolone glutamate (PA-G) is a neuroactive steroid that has been previously demonstrated to be a potent neuroprotective compound in several biological models in vivo. Our in vitro experiments identified PA-G as an inhibitor of N-methyl-D-aspartate receptors and a potentiator of γ-aminobutyric acid receptors (GABAARs).
Molecular mechanisms of sex differences in epilepsy and seizure susceptibility in chemical, genetic and acquired epileptogenesis
This article provides a succinct overview of sex differences in epilepsy and putative molecular mechanisms underlying sex differences in seizure susceptibility in chemical, genetic, and acquired epileptogenesis.
TRPM3 in brain (patho)physiology
Already for centuries, humankind is driven to understand the physiological and pathological mechanisms that occur in our brains. Today, we know that ion channels play an essential role in the regulation of neural processes and control many functions of the central nervous system.
Allopregnanolone and pregnanolone are reduced in the hippocampus of epileptic rats, but only allopregnanolone correlates with seizure frequency
Neurosteroids modulate epileptic activity by interacting with the γ-aminobutyric acid type A receptor, but their brain levels are still undetermined.
Neurosteroids and focal epileptic disorders
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids-allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)-are known to modulate GABAΑ receptor-mediated transmission, thus playing a role in controlling neuronal network excitability.
Longitudinal proneuroactive and neuroactive steroid profiles in medication-free women with, without and at-risk for perinatal depression: a liquid chromatography-tandem mass spectrometry analysis
Neuroactive steroids (NAS) are derivatives of cholesterol or steroidal precursors made in the gonads, adrenal gland, placenta and brain. We characterized longitudinal plasma proneuroactive and NAS in healthy perinatal comparison women (HPCW), women at-risk for perinatal depression (AR-PND), and women with PND with/without comorbid anxiety. We hypothesized that AR-PND women who either did or did not go on to develop PND would have elevated NAS concentrations as compared to HPCW and that NAS would be correlated to depressive and anxiety symptoms.
Neurosteroids and seizure activity
Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been continuously searched for. In this context, a group of endogenous or exogenous neurosteroids allosterically positively modulating GABA-A receptors may offer a promising approach.
Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics
Neurosteroids can modulate γ-aminobutyric acid type A receptor-mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α-dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE.
BV-2 microglial cells respond to rotenone toxic insult by modifying pregnenolone, 5α-dihydroprogesterone and pregnanolone levels
Neuroinflammation, whose distinctive sign is the activation of microglia, is supposed to play a key role in the development and progression of neurodegenerative diseases. The aim of this investigation was to determine levels of neurosteroids produced by resting and injured BV-2 microglial cells.
Steroids and Alzheimer’s disease: changes associated with pathology and therapeutic potential
Alzheimer's disease (AD) is a multifactorial age-related neurodegenerative disease that today has no effective treatment to prevent or slow its progression. Neuroactive steroids, including neurosteroids and sex steroids, have attracted attention as potential suitable candidates to alleviate AD pathology.
Stress and drug abuse-related disorders: the promising therapeutic value of neurosteroids focus on pregnenolone-progesterone-allopregnanolone pathway
The pregnenolone-progesterone-allopregnanolone pathway is receiving increasing attention in research on the role of neurosteroids in pathophysiology, particularly in stress-related and drug use disorders. These disorders involve an allostatic change that may result from deficiencies in allostasis or adaptive responses, and may be downregulated by adjustments in neurotransmission by neurosteroids.
TSPO ligands boost mitochondrial function and pregnenolone synthesis
Translocator protein 18 kDa (TSPO) is located in the mitochondrial outer membrane and plays an important role in steroidogenesis and cell survival. In the central nervous system (CNS), its expression is upregulated in neuropathologies such as Alzheimer's disease (AD).
Neurosteroid levels in patients with bipolar disorder and a history of cannabis use disorders
In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs).
A role of endogenous progesterone in stroke cerebroprotection revealed by the neural-specific deletion of its intracellular receptors
Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult.
Gender differences in susceptibility to schizophrenia: potential implication of neurosteroids
Past research has indicated gender differences in the clinical characteristics and course of schizophrenia.
Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat
Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism.
Pregnenolone does not interfere with the effects of cannabinoids on synaptic transmission in the cerebellum and the nucleus accumbens
The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ9-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication.
Microtubule associated protein 2 in bipolar depression: impact of pregnenolone
Pregnenolone, and related neurosteroids, may have antidepressant properties. Preclinical research proposes that microtubule associated protein 2 (MAP2) binding may be a mechanism for antidepressant properties of pregnenolone.
Adjunctive pregnenolone ameliorates the cognitive deficits in recent-onset schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial
This study aimed to examine the effect of add-on treatment with the neurosteroid pregnenolone (PREG) on neurocognitive dysfunctions of patients with recent-onset schizophrenia (SZ) and schizoaffective disorder (SA).
Neurosteroids and potential therapeutics: focus on pregnenolone
Considerable evidence from preclinical and clinical studies shows that steroids and in particular neurosteroids are important endogenous modulators of several brain-related functions.
Higher serum dehydroepiandrosterone sulfate protects against the onset of depression in the elderly: Findings from the English Longitudinal Study of Aging (ELSA)
Depression is one of the major causes of disability worldwide, but the complete etiology of depression is not fully understood. Dehydroepiandrosterone (DHEA) and its sulphated form DHEA(S) have been associated with mood and healthy aging.
The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity
The neurosteroids allopregnanolone and dehydroepiandrosterone (DHEA) are integral components of the stress response and exert positive modulatory effects on emotion in both human and animal studies.
Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial
Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA.
Pregnenolone can protect the brain from cannabis intoxication
Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated.
Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits
The neurosteroid allopregnanolone is a potent allosteric modulator of the gamma-aminobutyric acid type A receptor with anxiolytic properties. Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective functioning.
Pregnenolone for cognition and mood in dual diagnosis patients
Mood and substance-use disorders are both associated with cognitive deficits. Patients with mood and substance-use disorders have poorer cognition than patients with only a mood disorder. Pregnenolone may have beneficial effects on mood and cognition.
Neurosteroid regulation of central nervous system development
Neurosteroids are a relatively new class of neuroactive compounds brought to prominence in the past 2 decades.
Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics
Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics.
Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor
The neurosteroid pregnenolone (PREG) and its chemically synthesized analog 3beta-methoxypregnenolone (MePREG) bind to microtubule-associated protein 2 (MAP2) and stimulate the polymerization of microtubules.