. Author manuscript; available in PMC: 2023 Aug 23.

Published in final edited form as: Chem Res Toxicol. 2022 Aug 3;35(8):1312–1333. doi: 10.1021/acs.chemrestox.2c00072

Table 2.

Brain Neurotransmitter and Metabolite Levels Following PFAS Exposure in Animal Models^a

PFAS (PFAS/PFAS mixture) and dose	model/age of exposure/exposure duration	brain region	neurotransmitter or metabolite	dose-related change	source
PFOS: 0, 3.0, 6.0 mg/kg/d	male SD rats/adult/28 days	anterior hypothalamus	DA	increase	33
			DOPAC/DA	decrease
			HVA/DA	decrease
			GABA	increase
		mediobasal hypothalamus	DA	no change
			DOPAC/DA	no change
			HVA/DA	no change
			GABA	no change
PFOS: 0, 0.5, 1, 3, 6 mg/kg/d	male SD rats/adult/28 days	anterior hypothalamus	NE	increase	28
		mediobasal hypothalamus	NE	no change
		median eminence	NE	increase
PFOS: 0, 0.5, 1, 3, 6 mg/kg/d	male SD rats/adult/28 adults	anterior hypothalamus, mediobasal hypothalamus, and median eminence	5-HT	increase	29
PFOS: 0, 0.5, 1, 3, 6 mg/kg/d	male SD rats/adult/28 adults		5-HIAA/5-HT	decrease	29
PFOS: 0, 1.0, 10.0 mg/kg/d	female SD rats/adult/14 days	hypothalamus paraventricular nucleus	DA	no change	23
		hypothalamus paraventricular nucleus	NE	no change
		hypothalamus medial preoptic area	DA	no change
		hypothalamus medial preoptic area	NE	increase
PFOS: 0, 0.5, 1.0, 3.0, 6.0 mg/kg/d	male SD rats/adult/28 days	amygdala	DA	no change	34
			DOPAC	no change
			DOPAC/DA	no change
			HVA	decrease
			HVA/DA	no change
PFOS: 0, 0.5, 1.0, 3.0, 6.0 mg/kg/d	male SD rats/adult/28 days	prefrontal cortex^b	DA	no change^b	34
			DOPAC	no change^b
			DOPAC/DA	no change^b
			HVA	no change^b
			HVA/DA	no change^b
PFOS: 0, 250 mg/kg	male SD rats/adult/single dose	cerebrum	DA	no change	35
			5-HT	no change
			NE	no change
			GLU	no change
			GABA	no change
			GLY	no change
PFOS: 0, 1 mg/kg/d	SD rats (sex not specified)/development: gestational and postnatal/dosed GD1-PND21	cortex	ASP	increase	32
			SER	increase
			GLY	increase
			taurine	increase
			GABA	increase
PFOS: 0, 0.5, 1.0, 3.0, 6.0 mg/kg/d	male SD rats/adult/28 days	hippocampus	DA	increase	34
			DOPAC	no change
			DOPAC/DA	decrease
			HVA	no change
			HVA/DA	no change
PFOS: 0.00, 0.43, 2.15, 10.75 mg/kg/d	C57BL/6 mice (half male, half female)/adult/subchronic (3 months)	hippocampus	GLU	increase	27
PFOS: 0.00, 0.43, 2.15, 10.75 mg/kg/d		hippocampus	GABA	no change	27
PFOS: 0, 1 mg/kg/d	male C57BL/6 mice/development: postnatal/PND0-PND14/sampled at adulthood	dorsal hippocampus	GLU	increase	30
			GLN	no change
			GLY	no change
			GABA	increase
PFOS: 0.00, 0.43, 2.15, 10.75 mg/kg/d	C57BL/6 mice (half male, half female)/adult/subchronic (3 months)	dorsal striatum (caudate putamen)	DA	decrease	27
			DOPAC	decrease
			HVA	no change
			(DOPAC + HVA)/DA	no change
PFOS: 0, 250 mg/kg	male SD rats/adult/single dose	cerebellum, pons, and medulla	DA	no change	35
			5-HT	no change
			NE	no change
			GLU	no change
			GABA	no change
			GLY	no change
PFOS: 0, 1 mg/kg/d; 14 days from birth	male C57BL/6 mice/development: postnatal/PND0-PND14/sampled at adulthood	cerebellum	GLU	no change	31

			GLN	no change
			GLY	no change
			GABA	no change
PFOA: 0, 0.5, 2.5 mg/kg/d	male BALB mice/adolescent/28 days; 6 weeks-old at start	whole brain	DA	increase	36
			L-DOPA	increase
			5-HT	increase
			NE	decrease
			GLU	decrease
PFNA, PFDA, PFUA, PFDoDA, PFTrDA, PFTeDA, PFOA, PFOS, PFAS feed mix^C	male and female A/J mice/adolescent/10 weeks; PND21 at start	whole brain: females	DA	no change	25
		whole brain: males	DA	decrease	25
PFOS, PFTrDA, PFNA, PFOA	female juvenile Atlantic cod (G. morhua)/adolescent/once per week for 2 weeks	whole brain	DA	decrease	26
PFOS, PFTrDA, PFNA, PFOA		whole brain	DOPAC	no change	26
PFAS mix:^d low dose (1×) and high dose (20×)			DOPAC/DA	no change
			HVA	no change
			(DOPAC + HVA)/DA	no change
PFOA or PFOS: 0, 0.01, 0.1, 1.0 ppm (mg/L)	northern leopard frogs (Rana pipens)/development: larval/30 days	whole brain: PFOA	DA	decrease	24
		whole brain: PFOS	DOPAC	no change
			HVA	no change
			(DOPAC + HVA)/DA	increase
			NE	no change
			5-HT	no change
			5-HIAA	no change
			5-HIAA/5-HT	no change
			GLU	no change
			GABA	no change
			ACh	no change
PFOS alone or PFAS mix (PFOS, PFOA, PFHxS, PFPeA): 0, 10 ppb (0.01 mg/L); PFOS or PFAS mix (4.0 ppb PFOS, 1.25 ppb PFOA, 3.0 ppb PFHxS, 1.25 ppb PFHxA, 0.5 ppb PFPeA)	northern leopard frogs (Rana pipens)/development: larval or larval through metamorphosis/30 days during larval development or until metamorphosis was complete (juvenile frogs)	whole brain: PFOS, 30 days, larva	DA	no change	6
			DOPAC	no changeg
			HVA	no change
			(DOPAC + HVA)/DA	no change
			NE	no change
			5-HT	decrease
			5-HIAA	no change
			5-HIAA/5-HT	no change
			GLU	decrease
			GABA	no change
			GLU/GABA	no change
			ACh	no change
		whole brain: PFAS mix, 30 days, larva	DA	no change
			DOPAC	no change
			HVA	no change
			(DOPAC + HVA)/DA	no change
			NE	no change
			5-HT	decrease
			5-HIAA	no change
			5-HIAA/5-HT	no change
			GLU	decrease
			GABA	no change
			GLU/GABA	no change
			ACh	no change
		whole brain: PFOS, juvenile frogs; PFAS, mix juvenile frogs	DA	no change
			DOPAC	no change
			HVA	no change
			(DOPAC + HVA)/DA	no change
			NE	no change
			5-HT	no change
			5-HIAA	no change
			5-HIAA/5-HT	no change
			GLU	no change
			GABA	no change
			GLU/GABA	no change
			ACh	increase

Animal studies were included that assessed the effect of PFAS exposure on neurotransmitter levels and metabolite levels in the brain compared to vehicle controls. When multiple doses were included, a dose-related change was only included when significant changes were detecting with ascending doses. Studies that had no control group were excluded. Abbreviations: acetylcholine (ACh), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), gamma-aminobutyric acid (GABA), homovanillic acid (HVA), glutamate (GLU), glutamine (GLN), glycine (GLY), l-3,4-dihydroxyphenylalanine (L-DOPA), norepinephrine (NE), per- and polyfluoroalkyl substance (PFAS), perfluorodecanoic acid (PFDA), perfluorododecanoic acid (PFDoDA), perfluorohexanoate (PFHxA), perfluorohexanesulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), perfluoro-n-pentanoate (PFPeA), perfluorotetradecanoic acid (PFTeDA), perfluorotridecanoic acid (PFTrDA), perfluoroundecanoic acid (PFUA), postnatal day (PND), serotonin (5-HT), Sprague–Dawley (SD), and 5-hydroxyindoleacetic acid (5-HIAA).

Tissue degradation may have influenced results.

PFAS feed mix containing 2 ng/g PFNA, 3 ng/g PFDA, 3 ng/g PFUA, 8 ng/g PFDoDA, 16 ng/g PFTrDA, and 20 ng/g PFTeDA (6 d/wk) and gel diet containing 17.5 ng/g PFOA and 9.1 ng/g PFOS (1 d/wk).

PFAS injection mix low dose (1×) or high dose (20×) containing 25 or 500 mg/g PFOS, 16.95 or 339 mg/g PFTrDA, 5.925 or 118.5 mg/g PFNA, and 3.825 or 76.5 mg/g PFOA, respectively.