
SULDINA et al.924
BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026
and stearic acids at the sn-1 position, while in the
brain, phosphatidylcholine contains polyunsaturated
fatty acids at the sn-2 position, with docosahexaenoic
acid and arachidonic acid being the most common
in the human brain [1, 2]. It has been suggested that
this structural composition of phosphatidylcholine
in the brain in combination with the properties of
cholesterol and other PLs ensures conformation and
fluidity necessary for functional activity of the neuro-
nal membranes. Phospholipids are not only the main
component of cell membranes and transport mole-
cules but also serve as substrates and precursors for
a wide spectrum of biologically active molecules that
regulate metabolic pathways in the gut–brain axis
[4, 5]. In the central nervous system (CNS), PLs are
closely linked to the processes critical for neurome-
diation mechanisms, such as adenosine triphosphate
(ATP) production, mitochondrial transport, and pro-
duction and secretion of neurotransmitters. For ex-
ample, it has been estimated that oxidation of PLs
provides, on average, 20% of the total energy produc-
tion in the brain [6]. Phosphatidylcholine also serves
as a choline depot for the synthesis of the neurotrans-
mitter acetylcholine and, at the same time, acts as
a substrate for the synthesis of phosphatidic acid.
Sphingolipids, glycerophospholipids, and cholesterol
are involved not only in transmission of a spectrum
of cellular signals and formation of the lipid rafts,
maintaining energy and oxidative balance, but also
in axon myelination, blood-brain barrier formation,
and neuroinflammatory homeostasis regulation [6-8].
Phospholipids play an important role in synapse for-
mation, neurotransmitter release, and signal trans-
mission, and phospholipid metabolism deregulation
is closely associated with various neurodegenerative
diseases. Enzymes and co-factors of phospholipid me-
tabolism are considered as therapeutic targets [8, 9].
The membranes of synaptic vesicles consist of
phospholipids, with the largest proportions being
phosphatidylcholine, phosphatidylethanolamine, and
cholesterol. These phospholipids ensure physicochem-
ical properties of the neuronal membranes, which
are critical for neuromediation mechanisms [10, 11].
Phosphatidylserine and phosphatidic acid act as key
signaling phospholipids in regulation of the synaptic
vesicle cycle [11]. For example, phosphatidylserine in
the membrane of synaptic vesicles ensures interac-
tion with Rab and SNARE family proteins, providing
anchoring the synaptic vesicles at the presynaptic
membrane [10-12]. Additionally, phosphatidylserine
mediates initiation of synaptic exocytosis by the Ca
2+
sensor synaptotagmin-1, via its functional domains
(C2A and C2B) activation by phosphatidylserine only
in the presence of Ca
2+
[12]. Physicochemical proper-
ties of phosphatidic acid facilitate membrane bending
and instantaneous fusion upon neural impulse arrival.
Furthermore, phosphatidic acid acts as a critical co-
factor in stabilization of the synaptophysin complex,
as well as in positioning and activity of dynamin in
the mechanism of synaptic vesicles recycling [6, 8].
Deficiency of both phosphatidic acid and phosphati-
dylinositol, which are precursors for PI(4,5)P
2
, leads
to deregulation of the synaptic vesicles docking on
the presynaptic membrane, inhibiting their recycling
cycle, and thus impairing the neuromediation [6].
Connection between the regulation of the body’s
metabolic pathways and psychoemotional state has
become a highly relevant topic in the last decade.
A number of studies on the patients and animal
models indicate a much broader and more signifi-
cant influence than previously thought [13, 14]. Mod-
ern scientific paradigm of the gut–brain axis has un-
dergone significant evolution: from a model focusing
exclusively on microbiome, the emphasis has shifted
to studying metabolic pathways that mediate modu-
lation of the CNS functions by active components en-
tering with food: through interaction with the enteric
nervous system; through changes in the composition
of the gut microbiota; and through various mecha-
nisms of delivery of active metabolites and their sub-
sequent effect on molecular and cellular processes in
the brain [15, 16].
Previously, in the genetic model of chronic colitis
in mice with mutation in the Mucin-2 (Muc2) gene
it was shown that, on the one hand, there is a sig-
nificant change in the behavioral characteristics of
animals and, on the other hand, there is a change in
the metabolomic profile of intestinal and brain cells
[17, 18]. In Muc2 animals, social behavior disorders
were accompanied by the significant increase in the
levels of several forms of phospholipids in the intesti-
nal epithelial cells, most notably phosphatidylcholine,
phosphatidylserine, and phosphatidic acid [17]. Since
metabolism of phospholipids is critically important
for the brain function, and phospholipids can cross
the intestinal and blood-brain barriers in various
forms of packaging, we have then performed studies
that revealed a significant effect of the dietary intake
of both a phospholipid mixture (phosphatidylcholine,
phosphatidylserine, and phosphatidic acid) and soy
lecithin (70% total content of a phospholipid mixture:
phosphatidylcholine, phosphatidylethanolamine, phos-
phatidylinositol, and phosphatidic acid) on the social
and sexual behavior of mice [19, 20]. As a result, im-
pairments in social recognition and behavior, reduced
signs of compulsivity and anxiety, and increased ag-
gression in the males were observed with both long-
term and short-term intake of doses of soy lecithin by
the healthy animals, reproducing the findings of both
the same behavioral traits and the phospholipid en-
richment in the intestinal epithelium during chronic
inflammation in the Muc2 mice [17, 18].