The Alchemists of the Mind

Uncovering the Founders of Neurochemistry at the Sechenov Institute

Where Evolution Meets Chemistry

Imagine trying to decipher the brain's inner workings not as a static organ, but as a dynamic, evolving masterpiece shaped by millions of years. This was the revolutionary vision that birthed neurochemistry at the Sechenov Institute of Evolutionary Physiology and Biochemistry (IEPhB RAS). Named after Ivan Sechenov—the "Father of Russian Physiology" who discovered central inhibition in the brain—the institute became a cradle for pioneers who dared to merge physiology with chemistry ² ⁵ ⁹ .

At its heart stood Leon Orbeli, a scientific titan who, alongside disciples Evgeny Kreps and Andrei Polenov, unraveled how chemical dialogues between neurons, glia, and organs adapt across evolution, development, and disease ¹ ⁴ . Their work transformed neuroscience, proving that to understand the brain, we must speak the language of molecules.

The Architects of a New Neuroscience

Ivan Sechenov

The Intellectual Forge

Though Sechenov died decades before the institute's founding, his legacy was its bedrock. His 1863 monograph, Reflexes of the Brain, shattered conventions by proposing that all mental processes—even conscious ones—originate from reflex arcs ⁵ ⁹ .

1829-1905

Leon Orbeli

The Evolutionary Visionary

In 1956, Orbeli transformed a small laboratory into the Sechenov Institute of Evolutionary Physiology, anchoring it in a radical principle: nervous system functions can't be understood without studying their evolution ⁴ ⁸ .

1882-1958

Evgeny Kreps

The Lipid Detective

Orbeli's protégé, Kreps, took the helm in 1960 and expanded the institute's mission to include biochemistry—renaming it the Institute of Evolutionary Physiology and Biochemistry ⁴ . His obsession? Lipids, the enigmatic fats shaping neural membranes ¹ .

1899-1985

Andrei Polenov

The Neuroendocrine Cartographer

Polenov, another Orbeli disciple, mapped the brain's hormonal dialogues. His studies tracked how neurosecretory cells in the hypothalamus produce hormones like vasopressin, bridging neurons and glands ¹ .

1898-1981

Fun Fact: Sechenov's ideas were so radical that tsarist censors accused him of "debasing Christian morality" with materialism ⁶ .

Key Milestones

1863

Sechenov publishes Reflexes of the Brain, introducing the concept of central inhibition ⁵ ⁹ .

1956

Orbeli establishes the Sechenov Institute of Evolutionary Physiology ⁴ ⁸ .

1960

Kreps renames and expands the institute to include biochemistry ⁴ .

1981

Kreps publishes landmark studies on brain lipid composition across species ¹ .

Decoding a Landmark Experiment: Kreps' Lipid Revolution

Objective

To test if neural lipid composition reflects evolutionary complexity and functional specialization ¹ .

Methodology

Sample Collection: Brains from 5 species—octopus, frog, rat, dog, and human—were dissected.
Lipid Extraction: Tissues were homogenized in chloroform-methanol (2:1).
Chromatography: Lipids were passed through silica columns.
Fatty Acid Analysis: Phospholipids were saponified and analyzed via gas chromatography.
Statistical Comparison: Data normalized to brain weight and cell density.

Results & Analysis

Evolutionary Leap: Human cortices had 35% more phospholipids than octopus brains ¹ .
Neuron Specialization: Sensory neurons packed more plasmalogens (12% vs. 8% in motor neurons) ¹ .
Fatty Acid Uniqueness: Humans showed 15% "unique" fatty acids absent in invertebrates ¹ .

"Kreps proved lipid profiles are a 'molecular Rosetta Stone'—decoding how evolution crafts smarter brains through chemistry."

Table 1: Phospholipid Composition Across Species
Species	Total Phospholipids (mg/g tissue)	% Phosphatidylcholine	% Unique Fatty Acids
Octopus	18.7	42%	4%
Frog	22.3	48%	6%
Rat	28.9	51%	9%
Human (cortex)	35.2	55%	15%

Table 2: Lipid Profiles in Human Neuron Types
Neuron Type	Cholesterol (%)	Sphingomyelin (%)	Plasmalogens (%)
Motor Neurons	32%	15%	8%
Sensory Neurons	28%	22%	12%

The Scientist's Toolkit: Reagents That Unlocked Neurochemistry

Chloroform-Methanol (2:1)

Lipid extraction from neural tissues. Used for isolating membrane phospholipids ¹ .

Trypsin-EDTA solution

Dissociating neural cell clusters. Essential for preparing neuron-glia co-cultures ¹ .

Radioactive Choline (³H)

Tracing acetylcholine synthesis. Crucial for mapping neurotransmitter pathways ¹ .

Antibodies to Vasopressin

Labeling neurosecretory cells. Used for visualizing hypothalamic nuclei ¹ .

Ion Exchange Resins

Separating neurotransmitters. Key for quantifying GABA/glutamate ratios ³ .

Legacy: From Squid Synapses to Modern Medicine

Current Research Directions

Neurodegenerative Lipids: How lipid dysregulation fuels Alzheimer's ⁸
Stress Neurochemistry: Cortisol's synaptic impact across lifetimes ³ ⁸
Sensory Evolution: Molecular tweaks that adapt vision or hearing to environments ⁸

Impact Timeline

"The nervous system speaks in chemicals. Our task is to decipher its language." — E.M. Kreps, 1981 ¹

Kreps and Polenov trained generations of scientists, embedding Orbeli's creed: "To grasp function, trace its evolution." As we combat modern scourges like depression or dementia, we stand on the shoulders of these alchemists—who taught us that the brain's secrets are written in chemistry ¹ ⁴ .