Memory decline inhibitor containing lactic acid bacteria of the genus Lactococcus

Abstract

To provide means for suppressing the memory loss by a microorganism.SOLUTION: A memory loss inhibitor contains Lactococcus lactis subsp. cremoris H-61 strain (NITE P-92).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a memory decline inhibitor containing lactic acid bacteria of the genus Lactococcus, and a food and feed for inhibiting memory decline using the same.

Background Art

[0002] The population of elderly people aged 65 or over in Japan accounts for 28.1% of the total population (Cabinet Office, 2019). It is important for more than a quarter of the population, the elderly, to live healthy and independent lives in order to maintain Japan's medical and welfare services and improve the quality of life of the entire nation.

[0003] A major cause threatening the independent lives of the elderly is the decline in cognitive function. Cognitive function consists of multiple functions such as memory, attention, and language ability. Among them, the peak of memory is as early as the late teens. People begin to notice a decline in memory such as "not being able to remember names" from middle age, and the frequency increases with aging. When the decline of memory progresses pathologically, one forgets having eaten breakfast or the faces of very familiar people, which is so-called dementia, and it becomes difficult to live a self-disciplined life. Prevention of memory decline is one of the important factors for maintaining the quality of life.

[0004] It has been reported previously that such memory decline can be prevented by microorganisms such as lactic acid bacteria. For example, there is a report that the decline of memory was suppressed by feeding viable bacteria of Lactobacillus paracasei PS23 strain to aging-accelerated mice for 12 weeks (Non-Patent Document 1). In addition, there is a technique for suppressing age-related learning and memory impairment by administering one or more microorganisms or cultures belonging to the genus Lactobacillus, the genus Bifidobacterium (Bifidobacterium), the genus Streptococcus, the genus Leuconostoc, and the genus Pediococcus (Patent Document 1).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Literature

[0006]

Non-Patent Literature 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] All the tests using the above-mentioned Bifidobacterium genus, Streptococcus genus, Leuconostoc genus, and Pediococcus genus, including Lactobacillus paracasei PS23 strain of lactic acid bacteria, have been conducted with live bacteria (Non-Patent Literature 1, Patent Literature 1). Since maintaining live bacteria requires a temperature and moisture suitable for each bacterium, there are limitations to the objects to which the bacteria can be added to food or feed. Furthermore, temperature control is essential even during the distribution and storage of the added products, and the labor involved is passed on to the product price. On the other hand, if it is a dead cell powder, it can be stored at room temperature, and it is also easy to make food additives, tablets, etc. In order to realize a memory impairment preventive agent that is inexpensive and can be used in various situations, dead cell powder is desirable.

[0008] Furthermore, the technology for suppressing learning and memory impairment reported in Patent Literature 1 is reported based on a 4-day test using Caenorhabditis elegans. There remains doubt about applying the findings of Caenorhabditis elegans, which is phylogenetically far removed, to mammals regarding the effects on higher brain functions such as learning and memory.

[0009] As described above, although there is already a technology for preventing memory decline by microorganisms, there has been no knowledge about those using easily handled dead cells. The present invention has been made under such a technical background, and an object thereof is to provide a novel means capable of suppressing memory decline by dead cells of microorganisms.

Means for Solving the Problems

[0010] As a result of intensive studies to solve the above problems, the present inventors have found that the dead cell powder of the lactic acid bacterium Lactococcus lactis subsp. cremoris H-61 strain has an effect of suppressing memory decline. Since the effect of suppressing memory decline of the H-61 strain has been confirmed by tests using mice, it is considered to be effective also for humans, who are the same mammals. In the H-61 strain, inhibitory effects on bone density decline (Japanese Patent Application Laid-Open No. 2006-256993), hair loss (Japanese Patent Application Laid-Open No. 2015-187171), and hearing loss (Oike et al., Sci Rep 6: 23556, 2016) associated with aging have already been reported, but all of them are suppression of aging in peripheral tissues. The inhibitory effect on aging (suppression of memory decline) acting on the central nervous system as provided by the present invention in the H-61 strain has not been reported so far. The present invention has been completed based on the above findings.

[0011] That is, the present invention provides the following (1) to (4). (1) A memory decline inhibitor characterized by containing the lactic acid bacterium Lactococcus lactis subsp. cremoris H-61 strain (NITE P-92).

[0012] (2) The memory decline inhibitor according to (1), wherein the lactic acid bacterium Lactococcus lactis subsp. cremoris H-61 strain (NITE P-92) is a dead cell.

[0013] (3) A food for suppressing memory decline, characterized by containing the memory decline inhibitor according to (1) or (2).

[0014] (4) A feed for suppressing memory decline, characterized by containing the memory decline inhibitor according to (1) or (2).

Effect of the Invention

[0015] The present invention provides a novel memory decline inhibitor. Since the memory decline inhibitor of the present invention can also use dead cell powder, it is inexpensive and can be used in various scenarios. In addition, the H-61 strain contained in the memory decline inhibitor is classified as a coccus and has a smaller cell size than bacilli. Therefore, it also has the advantage of being more easily taken up from the intestinal tract compared to the prior art (PS23 strain, Non-Patent Document 1) that uses bacilli.

Brief Description of the Drawings

[0016]

Figure 1

Figure 2

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Modes for Carrying Out the Invention

[0017] Hereinafter, the present invention will be described in detail. The memory decline inhibitor of the present invention is characterized by containing Lactococcus lactis subsp. cremoris H-61 strain (hereinafter, sometimes simply referred to as "H-61 strain").

[0018] The H-61 strain is deposited as follows. 1) Name and address of the depository institution Name: National Institute of Technology and Evaluation, Patent Microorganisms Depositary Address: 2-5-8 Kazusa Kamashima, Kisarazu City, Chiba Prefecture, Japan 292-0818 2) Date of deposit: March 14, 2005 3) Accession number: NITE P-92

[0019] The H-61 strain may use viable bacteria or dead bacteria, but it is preferable to use dead bacteria that can be stored at room temperature and are easy to handle. When using the H-61 strain as viable bacteria, the culture of the H-61 strain may be used directly as a memory impairment inhibitor, or a culture that has been treated by conventional methods such as concentration, washing, purification, sterilization, pH adjustment, deodorization, and decolorization may also be used. The culture of the H-61 strain can be obtained, for example, by culturing in a TYG medium or the like for about 1 to 2 days under facultative anaerobic conditions. In addition, the bacterial cells can be collected from the culture by centrifugation, and can also be washed 1 to 2 times with physiological saline or sterilized water and then used. When using the H-61 strain as dead bacteria, the above-mentioned culture or bacterial cells can be heat-sterilized and, if necessary, powdered and used.

[0020] For the formulation of the memory impairment inhibitor of the present invention, pharmaceutically acceptable excipients, binders, disintegrants, lubricants, flavoring agents, suspending agents, coating agents, etc. may be appropriately mixed. Dosage forms can include tablets, capsules, granules, powders, powders, syrups, etc. The administration method is not particularly limited, but oral administration is preferred.

[0021] The dosage of the memory impairment inhibitor of the present invention is not particularly limited as long as it can exert a memory impairment inhibitory effect. For example, for humans, administration at a dose of 0.5 to 10 mg / kg / day in terms of bacterial cell weight, preferably about 1 to 8 mg / kg / day is appropriate. The number of administrations is not particularly limited, and it can be administered once a day or divided into several times.

[0022] The memory impairment inhibitor of the present invention can be used as a memory impairment preventive agent (when used at a time when no obvious memory impairment is observed) or as a memory impairment therapeutic agent (when used at a time when memory impairment is observed).

[0023] The memory decline inhibitor of the present invention can also be incorporated into foods to impart the memory decline inhibitory effect to these foods. Examples of foods include dairy products (e.g., cheese, fermented milk, lactic acid bacteria beverages, butter, powdered milk, etc.), beverages (e.g., milk beverages, fruit juice beverages, soft drinks, etc.), confectioneries (e.g., jelly, candy, butter cake, etc.), and processed egg products (e.g., pudding, mayonnaise, etc.). Further, the memory decline inhibitor of the present invention can be incorporated into feeds to impart the memory decline inhibitory effect to these feeds. Suitable examples of feeds include feeds (pet foods) for animals raised as pets (e.g., dogs, cats, hamsters, rabbits, etc.).

Example

[0024] Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0025] <Method> Twenty-four female accelerated aging model mice were divided into a control group (12 mice) and an H-61 administration group (12 mice). The control group was allowed to freely consume normal feed. The H-61 administration group was allowed to freely consume feed containing 0.05% of heat-killed H-61 lactic acid bacteria powder from 1.5 months of age.

[0026] After the start of ingestion, the novel object recognition test was conducted 4 times from 2 months of age to 13 months of age. This test is a memory test that utilizes the characteristic of rodents to prefer novel objects. Mice with better-preserved memory prefer novel objects different from the objects they have seen before and explore them for a longer time (Figure 1). At 14 months of age, memory was evaluated using the Barnes maze task. In this task, mice that dislike bright and open places are made to learn the location of a dark and narrow goal box. Then, the box is removed and they are allowed to freely explore the maze (Figure 2). Individuals that spend a longer time exploring the area where the goal box was installed indicate better memory.

[0027] <Results> Figure 3 shows the ratio of the exploration time for novel objects in the novel object recognition test. The higher the value, the longer the exploration time for novel objects compared to known objects. At 10 months and 13 months, the novel object exploration rate in the H-61 administration group was significantly higher than that in the control group (P<0.05).

[0028] Figure 4 shows the time spent exploring the area (1 / 4) where the goal box was installed in the Barnes maze task. The goal area exploration time in the H-61 administration group was significantly longer than that in the control group (P<0.05).

[0029] The above two results indicate that the administration of the H-61 strain suppressed the memory decline associated with aging. This technology is the first memory decline inhibitor using Lactococcus microorganisms. Also, in the novel object recognition test conducted over time, the H-61-administered mice showed a memory level comparable to that of 2-month-old mice even at 13 months of age. The H-61 strain may be able to suppress the memory decline perceived from middle age by ingestion from the young age.

Industrial Applicability

[0030] The present invention can be used in industries related to pharmaceuticals, foods, and feeds.

Claims

1. A memory decline inhibitor characterized by containing Lactococcus lactis subsp. cremoris strain H-61 (NITE P-92).

2. The memory decline inhibitor according to Claim 1, wherein Lactococcus lactis subsp. cremoris strain H-61 (NITE P-92) is a dead cell body.

3. A food for inhibiting memory decline, characterized by containing the memory decline inhibitor according to Claim 1 or 2.

4. A feed for inhibiting memory decline, characterized by containing the memory decline inhibitor according to Claim 1 or 2.

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