DMSO Autism Studies
When writing articles, I try to trim down each study I include to their bare essentials to keep them from being too long. As some readers may be interested in reviewing the individual summaries of the DMSO autism studies I am including them here.
M100907 (5-HT2A receptor antagonist; 0.1 mg/kg IP) significantly attenuated repetitive self-grooming behavior in BTBR mice (reduced grooming duration to levels comparable to B6 controls, p<0.01 vs. vehicle-treated BTBR), while 0.01 mg/kg showed no effect; M100907 at either dose had no effect on grooming in B6 mice or locomotor activity in BTBR or B6 mice, indicating selective reduction of repetitive behaviors without general motor suppression.
DMSO served as the subcutaneous injection control for estradiol replacement therapy in ovariectomized (OVX) C57BL/6 female mouse observers. The OVX mice showed deficient empathic consolation behavior (reduced allolicking/allogrooming [ALAG] total time and bouts) and absent observational contagious pain (OCP). Estradiol at 2.0 μg subcutaneously (versus DMSO control) significantly restored empathic consolation-like behavior and OCP, and significantly increased peripheral blood arginine vasopressin (AVP) concentration compared to DMSO control (P = 0.042). Because the DMSO control group showed the deficit phenotype while the estradiol (dissolved in DMSO) group showed restoration, the DMSO+estradiol combination produced the therapeutic effect. Subcutaneous injection. OVX C57BL/6 female mouse model of empathy deficit, multiple groups (n = 6 per group).
In a prenatal rat model of autism induced by valproic acid (VPA), researchers demonstrated that resveratrol (RSV), administered subcutaneously from embryonic day 6.5 to 18.5 and dissolved in DMSO as the vehicle, effectively prevented key molecular and behavioral autistic-like features. Notably, the combination of DMSO plus resveratrol maintained its protective efficacy against VPA-induced autism-like phenotypes, even though prenatal DMSO exposure alone produced a significant reduction in dendritic spine density and number in the medial posterodorsal subnucleus of the medial amygdala (MePD). This finding indicates that the beneficial preventive effects of resveratrol on autistic-like behaviors were not impaired by the observed structural changes in the MePD. The study therefore supports the potential of resveratrol as a promising prenatal intervention strategy for mitigating autism-like outcomes in this well-established animal model, while also underscoring the importance of understanding the independent bioactive effects of common solvents like DMSO in neurodevelopmental research.
The study investigated the neuroprotective and anticonvulsant potential of prenatal resveratrol (RSV) treatment in preventing behavioral alterations characteristic of autism spectrum disorder (ASD) in the valproic acid (VPA)-induced rat model; pregnant Wistar rats were divided into four groups (control: vehicle only; RSV: RSV + vehicle; VPA: vehicle + VPA; RSV+VPA: RSV + VPA), with prenatal VPA exposure (i.c.v. 2.4 mg/µL) used to induce ASD-like phenotypes; male offspring underwent behavioral testing: nest-seeking (P10, sensory discrimination), three-chamber sociability/novelty (P67, social interaction/preference), and Y-maze (P30–P40, learning/strategy shifting); RSV partially prevented VPA-induced deficits in nest-seeking discrimination (improved success ratio) and three-chamber social/novelty behaviors (restored preference for novel conspecifics), but did not significantly affect Y-maze learning or strategy shifting; hippocampal histology (cresyl violet) and GluR1 immunohistochemistry suggested RSV modulated excitotoxicity/plasticity pathways; results indicate RSV counteracts some VPA-induced ASD-like behaviors (sensory/social domains), supporting glutamatergic system involvement and RSV’s therapeutic potential for ASD-related deficits; DMSO was used operationally as the vehicle control for RSV and VPA prenatal administration, ensuring vehicle-specific effects were distinguished from those of the compounds in the autism model behavioral and histological assessments.
Neonatal curcumin treatment improved autism-related behaviors in BTBR mice by enhancing sociability, reducing repetitive behaviors, and restoring hippocampal neurogenesis, including neural progenitor cell proliferation and differentiation; DMSO was used solely as a solvent control.
Epothilone D treatment in BTBR mice improved autism-like repetitive behaviors by stabilizing microtubules and modulating excitatory synapse– and myelin-related protein expression, suggesting microtubule stabilization as a potential therapeutic approach for autism spectrum disorder.
DMSO (0.1% in PBS) was co-administered intraperitoneally with curcumin (50 mg/kg) to autistic model rats for 3 weeks, serving both as the curcumin vehicle and as the solvent control for the VPA-C group. The curcumin+DMSO combination significantly increased hippocampal neuron counts in dentate gyrus (DG) and cornu ammonis 3 (CA3) regions compared to the VPA-C group (P < 0.05), decreased astrocyte numbers (P < 0.05), increased social communication behaviors (P < 0.05), and improved learning and memory. The VPA-C group received equal amounts of 0.1% DMSO in PBS but showed no improvement versus the untreated VPA model, so the therapeutic effect is attributable to curcumin delivered in DMSO. Intraperitoneal injection. Wistar rats, sodium valproate-induced autism model, 100 model rats plus controls.
DMSO served as vehicle control for intraperitoneal injection of epothilone D (3 mg/kg, weekly for 8 weeks) in BTBR mice, a model of autism spectrum disorder. Epothilone D reduced self-grooming times, increased social ability, improved microtubule stability, increased excitatory synapse number, and enhanced myelin basic protein (MBP) expression in the cerebral cortex. Intraperitoneal injection. Eight-week-old BTBR mice, autism model.
DMSO (1% in physiological saline) served as the solvent for baicalin and was administered as the vehicle control to the VPA model group and NS (normal) group by gavage from postnatal day 14–35. Baicalin at 60, 80, and 100 mg/kg improved learning and memory in valproic acid (VPA)-induced autism model rats, with 100 mg/kg showing the best results: significant improvements in new object recognition, Y-maze alternation (P<0.05), and Morris water maze escape latency (P<0.05), increased NeuN-positive cells in hippocampal CA3 region (P<0.05), and promoted brain-derived neurotrophic factor (BDNF) protein and mRNA expression and tyrosine kinase receptor B (TrkB) mRNA expression in the hippocampus. Intragastric administration. Wistar rat offspring, prenatal VPA (600 mg/kg) autism model, 25 rats per group.
DMSO served as the vehicle control for intraperitoneal injection in the control group of BTBR mice (a model of autism spectrum disorder). Epothilone D (3 mg/kg, weekly for 8 weeks) improved restricted repetitive behaviors in marble burying tests compared to DMSO-treated controls, increased stable tubule-only polypeptide (STOP) protein expression, and increased post-synaptic density (PSD) thickness in the cerebral cortex (P<0.05–P<0.01). Intraperitoneal injection. BTBR mice, autism spectrum disorder model, 8-week-old.
DMSO served as the vehicle control for stereotactic injection of Wortmannin (phosphoinositide 3-kinase (PI3K) inhibitor) into the prefrontal cortex of valproic acid (VPA)-exposed male offspring mice modeling autism spectrum disorder (ASD). Wortmannin injection improved ASD-like behaviors, rescued dendritic spine density, down-regulated the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and upregulated synaptic proteins postsynaptic density protein 95 (PSD95) and phosphorylated synaptophysin (p-Syn). Stereotactic intracerebral injection. Prenatal VPA-exposed ASD model in male C57 mice (n=10 per group).
DMSO (0.1% v/v) served as the vehicle control for Epothilone D treatment of primary cortical neurons from BTBR autism-model mice. Compared to the DMSO control, 10 nM Epothilone D increased microtubule cold stability, upregulated excitatory synapse-related proteins (VGLUT1, PSD95, GluN2B, mGluR5) and microtubule-associated proteins (Acetyl-Tubulin, MAP2, STOP), and increased dendritic spine density, suggesting microtubule stabilization improves excitatory synaptic structure in the autism model. In vitro study.
DMSO served as a minor component (1 ml/L) in the PBS vehicle for curcumin and was also present in the normal and model group vehicle injections. Curcumin (50 mg/kg i.p. for 3 weeks) increased hippocampal neuron counts and decreased astrocyte numbers (P<0.05) in valproate-induced autism model rats. Intraperitoneal injection. Wistar rats, sodium valproate-induced autism model (n=10 per group, 28-day-old).
DMSO (5%) served as a solvent control for stereotactic injection of melatonin and Wortmannin into the prefrontal cortex of CTNND2-knockout mice. Melatonin (10 mg/kg, oral gavage) improved ASD-like behaviors, promoted synapse-associated protein synthesis (p-Syn, ELKS, PSD95), and improved dendritic spine development by upregulating the PI3K/Akt/mTOR signaling pathway in the prefrontal cortex. Intraperitoneal and intracranial injection; oral gavage. CTNND2-/- autism model mice (multiple groups of n=not specified per group).
DMSO (0.1%) served as the intraperitoneal injection vehicle control for curcumin (20 mg/kg) administered from postnatal day 6 to 8 in BTBR mice. Neonatal curcumin treatment promoted hippocampal neural progenitor cell proliferation, increased radial glial cells in the subgranular zone, enhanced newborn neuron maturation, and improved social behaviors and reduced repetitive behaviors in the BTBR mouse model of autism. Intraperitoneal injection. BTBR T+Itpr3tf/J mouse model of autism spectrum disorder and C57BL/6J controls.
DMSO (in 0.9% saline) served as the vehicle control for intraperitoneal injection of W146 (S1PR1 antagonist, 1 mg/kg daily for 21 days) in BTBR mice, a model of autism spectrum disorder. BTBR mice showed significantly elevated hippocampal S1P and S1PR1 compared to C57 controls (P < 0.01). W146 treatment improved learning and memory in the Morris water maze, reducing escape latency and increasing platform crossings (P < 0.05), increased phospho-CaMKII and phospho-CREB expression in the hippocampus, preserved hippocampal CA1 neuronal density, maintained microvascular integrity (increased CD31 expression), and reduced neuronal apoptosis via decreased phosphorylated ERK (P < 0.05) and Caspase-3 expression. Intraperitoneal injection. Four-week-old male BTBR T+tf/J mice and C57BL/6J controls (n = 16 per group).